14
May
2020

Meet My Friend Who Supported Trump in 2016

Luke Timmerman, founder & editor, Timmerman Report

[This week, I’m re-publishing this column written Nov. 9, 2016. It’s probably more important to read now.—Luke]

I’ve been dreading this moment since June. That’s when I started telling people: Trump was going to win. I could feel it in my bones, because of where I’m from.

We’ve heard enough by now that the elites have let us down. The elites in politics, business, and the media couldn’t see what Donald Trump was tapping into. Most of these successful people (including you) live in islands of prosperity, coastal cities full of highly educated folks doing interesting work. The economy is improving in those places. The future looks bright, right?

The electoral map tells us a different story. Vast geographic stretches of people voted red, for a guy who ran as an authoritarian candidate, not a traditional Republican. It’s a powerful statement against the establishment.

I know these voters well. I spent the first 18 years of my life growing up on an 80-acre family farm in Grant County, southwestern Wisconsin. I grew up driving tractors, shoveling pig shit, and spreading it as fertilizer on corn fields.

All around me were people who owned guns, went deer hunting, did manual labor, and told off-color jokes. Most of these people were interested in family and traditional values. They weren’t that interested in advancing the causes of historically disadvantaged groups—women, minorities, gays. While I was fortunate to grow up in a stable, loving, two-parent family, I recognize the environment painted by J.D. Vance in his excellent memoir “Hillbilly Elegy.”

When I went to college in the liberal haven of Madison, Wisconsin, and pursued a career in journalism, I left most of that world behind. I stayed in touch with my family and a small group of high-school friends. But, essentially, I emigrated from working class, blue collar, rural America to wealthy, elite America.

It’s VERY rare for someone from my socioeconomic background to travel the journey I’ve traveled. Almost nobody I know in journalism or biotech grew up on a farm, qualified for reduced-price lunches at school, or came from a blue-collar family like me. They came mainly from the suburbs, from more privileged backgrounds.

These days, I spend my time in a very privileged zone. Running this newsletter, writing for Forbes, and hosting the Signal podcast means interacting with people who graduated from Ivy League schools, CEOs of companies, and high-level government officials. After a while, it gets comfortable. Normal. It’s easy to forget where you come from.

Even for me, living in urban, liberal Seattle, it’s easy to quickly become blind to vast swaths of America.

Until this past summer, when I had a deep, two-hour conversation with a friend I’ve known since middle school in Platteville, Wisconsin. I’ll call him J.

He is in his early 40s, with two teenage kids, living in a western state. He’s a skilled tradesman who installs sports equipment for schools and churches. He makes a decent middle-class living, and he travels the country on jobs. He also does a little driving on the side for Uber. He’s alone a lot while traveling, and he listens to a lot of conservative talk radio.

J sat in my living room and talked at length, in matter-of-fact tones, about why he was supporting Trump. I told him I strongly disagreed, but I didn’t try to talk him out of it. I decided this was a time for me to listen, and for him to talk.

“The system is broken. Corrupt.”

“We need to blow the whole thing up. Push the reset button.”

“It can’t get any worse.”

“Trump’s not perfect, but he’s not beholden to anyone.”

This kind of apocalyptic view didn’t seem to square with his economic experience. J doesn’t have a college degree, but he’s done well financially for himself and his family. We’ve both flown to Pasadena to watch our beloved Wisconsin Badgers play in the Rose Bowl more than once. J’s experience tells me Trump’s appeal is cultural more than economic.

Despite J’s economic success, he has some serious anxiety and resentment beneath the surface. He rails against the popular notion that “everybody must get a college education” to get ahead, that the economy should be only knowledge-based. This has been an uplifting message of both political parties for a long time. That cultural value system, and programs to advance that policy objective, have created a lot of opportunity for people who previously had limited educational opportunity.

It also has created a downside: People like my friend J feel like second-class citizens because of a lack of college education. He feels condescended to in the media, and laughed at in sit-coms and movies. Conservative talk radio fans the flames. Think about how many people who work in construction, at the post office, in the trash hauling business, feel the same way. They want a president who takes them seriously.

It would be easy to write off my friend J as narrow-minded and simple. That’s where too many elites go wrong. He may not be formally educated, but he’s one of the most curious people I know – much more curious about biotech than most college-educated people. J always wants to hear about the exciting advances I’m writing about in biotech. He pulls out his iPhone and avidly listens to the Signal podcast.

After one show on the rise of superbugs, he wrote:

I really wish that kind of topic would make more news.  People really have no clue how much damage can be done to themselves and others.  It’s good that the medical community is getting on top of it, but the public really needs to be educated. My biggest complaint with your podcast is there is not enough of them.

These are the words of someone who cares about his country, cares about issues, just like I do. He’s not a wingnut.

There certainly are angry people out there, and many of them have reason to be angry at the establishment. When I drove my family hundreds of miles across the American West this summer to vacation in Yellowstone National Park, I saw some troubling things. There were destitute run-down buildings in Montana, where heroin and oxycodone was easy to spot.

In eastern Idaho, I saw a giant Confederate flag hoisted above the American flag. Further down that same junk-strewn highway, when I stopped for lunch with my African-American wife and daughter, a man driving a sport-utility vehicle gave me a 30-second, intimidating staredown.

Message: Your kind isn’t welcome here.

These people are being left behind, and that’s not right.

Today, after the Trump victory, my friend J was cautiously optimistic. “At the very least, it is a massive shake up to our political system, that definitely needs the shaking,” he wrote.

The pharmaceutical industry may be breathing easy today, knowing that Clinton’s drive to corral drug prices has been squashed. Thoughtful people in this industry are working on solutions focused on people in red America, but there aren’t enough.

This industry would be wise to remember that it serves the whole country, the whole world. It’s easy to get comfortable with the tiny slice of elite investors, elite media, elite physicians, and elite scientists we know personally. It’s easy to forget everyone else.

As people re-assess the pharma industry’s social contract, it’s important to remember just how big a place the world is.

Now on to the highlights of the week in biotech

Story of the Week

  • An Outbreak of Severe Kawasaki-like Disease at the Epicenter of the SARS-CoV-2 Epidemic in Italy. Observational Cohort Study. The Lancet. May 13. (Lucio Verdoni et al).

This, in my view, was the single most disturbing scientific report of the week. Turns out kids aren’t bulletproof to COVID19, after all. This new cohort study from Italy reinforces a similarly mysterious case series of massive inflammation and multi-organ failure in kids in New York City, which was closely followed by corroborating reports from doctors in France.

This toxic shock syndrome in kids is deeply worrying to parents. It could also be an eye-opener for the large and vocal faction in the US that has been arguing that we should shrug off the pandemic partly because “oh, it’s just old people dying.” We can’t shrug off the virus and turn the clock back to 2019. That’s not going to happen. People are dying. Many more will die because of our inaction and incompetent federal leadership. As a result, we have to come to terms with a new way of life.

It’s up to us how we reinvent the world.

The Wild West

  • “After Wisconsin court ruling, crowds liberated and thirsty descend on bars. ‘We’re the Wild West,’ Gov. Tony Evers says.” (See Washington Post coverage with infuriating pictures).

Compare that with the NYT caseload chart for Wisconsin. The rate of new cases in Wisconsin is slowing. Good. But the bear hasn’t yet been wrestled to the ground. The virus is nowhere close to contained.

It’s way too early to declare victory and hit the bars. Based on what we know about the epidemiology, you can set your calendar for an increase in cases in Wisconsin in 2-3 weeks. Part of me wants to scream at the people who are jamming themselves in, elbow-to-elbow into the bars without masks. Many probably don’t know anyone with COVID19. Many probably think the media elites are manufacturing fear and controversy. Many want to “own the libs.” Many take delight in thumbing their noses at Gov. Tony Evers, a Democrat who had extended the state’s stay-home order, until it was struck down by the conservative majority on the Wisconsin Supreme Court.

Many of these protesting citizens also know 85,000 are dead, the death toll grows every day, and that’s terrible.

But people do seem to forget many relevant facts. Such as:

  • As of mid-May, we are still way behind on testing, with about 320,000 nationwide performed per day (compared to the target of 5 million a day a Harvard team has said we need to be doing by early June).
  • Based on serology testing to date in hotspots, most epidemiologists believe we probably have 10 times as many cases in the US than the 1.4 million currently confirmed.
  • People also seem to forget that asymptomatic people spread the disease – i.e. we likely have millions of people who have no idea they are sick who are out and about infecting others.
  • Many people probably don’t realize the emerging risk for kids. It might take a few weeks for the reports about toxic-shock syndrome in children in New York, Italy, and France to sink in.

It’s a lot to ask members of a free society to stay up-to-the-minute on all the fast-moving science news. Especially when so many have been coached to distrust everyone and everything. But now that quite a few people seem to think they’ve “sacrificed enough” and it’s time to hit the bars, we have to brace ourselves for a lot more sacrifice.

Science

  • Should COVID19 Take Advice from Rheumatologists? The Lancet. May 7. (Kate Kernan and Scott Canna)
  • Performance of the rapid Abbott ID NOW, the 5-minute Test for SARS-CoV-2 Infection in nasopharyngeal swabs and dry nasal swabs (It was basically useless). BioRxiv. May 12. (Atreyee Basu et al at NYU Langone Health). Abbott questioned the study methods.
  • Seroprevalence Study Shows 5% of Spaniards Have Antibodies to Coronavirus, and 90% of Infections Were Undetected by Healthcare System. El Pais. May 14. (Borja Andrino et al)

Science Features

  • Legendary Virologist Peter Piot, Who Fought HIV and Ebola, on His Near-Death Experience with COVID-19. Interview with Science. May 8. (Dirk Draulans)
  • One Benefit. The Expansion of Telemedicine. NYT. May 11. (Jane Brody)
  • This Supernova in Human History Will Need Many Perspectives to Understand. STAT. May 14. (Vinay Prasad and Jeffrey Flier)
  • Everything You Need to Know About Herd Immunity. Elemental. May 13. (Tara Haelle)
  • How Gilead Prepared for the Big Moment with Remdesivir. Bloomberg News. May 14. (Robert Langreth)
  • COVID19 Brings Health Disparities Research to the Forefront. NIH Director Blog. May 14. (Francis Collins)

Testing

  • The Testing Strategy We Need to Reopen Safely. Time. May 13. (Scott Gottlieb)

Treatments

  • Monoclonal Antibodies. Why Are You Optimistic? In the Pipeline. May 14. (Derek Lowe)
  • Hydroxychloroquine in 150 Hospitalized Patients in China. A Failed Randomized Study. BMJ. (Wei Tang et al)

Investigations

Policy & Politics

  • Official CDC Reopening Guidelines for States, Silenced by the White House. (Full document)
  • Highlights of Tony Fauci Congressional Testimony. STAT. May 12. (Lev Facher)
  • To Restart Business, Protect Workers. Bloomberg Opinion. May 11. (Michael R. Bloomberg)
  • We’re Retreating. Let’s Call the New COVID19 Strategy What It Is. Washington Post. May 13. (Leana Wen)
  • We Need to Enter the Fifth Stage of Coronavirus Grief: Acceptance. The Sooner We Accept the New Normal, the Sooner and Safer Reopening Will Be. Washington Post. May 14. (Tom Frieden)
  • Rick Bright Warns The Crisis Will Worsen Without Fast Federal Action. Politico. May 14. (Sarah Owermohle and Dan Diamond)

Strategy

  • Long Range Planning Reframed as “Leaders Require Purpose.” LifeSciVC. May 8. (Rene Russo)
  • Why Big Investors Aren’t Betting It All on a Coronavirus Cure. WSJ. May 14. (Gregory Zuckerman)

Vaccines

The Dysfunctional US Health Care System

  • Why 1.4 million US Healthcare Jobs Have Been Lost During a Huge Health Crisis. NYT Upshot. May 8. (Margot Sanger-Katz)
  • America’s True COVID19 Death Toll Already Exceeds 100,000. NYT. May 13. (Nicholas Kristof)

Manufacturing and Access

  • Gilead Signs Deals with 5 Generic Manufacturers in India and Pakistan to Boost Remdesivir Production. (Gilead statement)
  • HHS Announces US Distribution of Remdesivir to Certain States. May 9. (HHS statement)
  • France Says It Would Be ‘Unacceptable’ if Sanofi Provides a COVID19 Vaccine to the US Market First. May 14. Agence France-Presse.

Thinking Big

Illumina and Genomics England are teaming up on a study across the UK’s National Health Service. They’re doing whole genome sequencing on 20,000 people currently or previously in an intensive care unit with SARS-CoV-2, plus another 15,000 people with mild or moderate symptoms.

Personnel File

Dr. Michelle McMurry-Heath was named the new president and CEO of the Biotechnology Innovation Organization. She replaces Jim Greenwood on June 1. Dr. McMurry-Heath represents quite a turn in direction at the industry trade group. She has outstanding credentials as a physician-scientist. She has experience at the FDA and in regulatory affairs at Johnson & Johnson. She’s African-American. She speaks about social justice. All of this makes for a strikingly different background than her predecessor, who came to BIO primarily because of his political relationships and knowledge from the years when he was a Republican member of Congress from Pennsylvania. I don’t know Dr. McMurry-Heath. But I am happy to see a black person get the top job at BIO, and am eager to see what she does in this role. See STAT’s coverage of the new BIO leader.

Moncef Slaoui was tapped to head up the vaccine effort for Operation Warp Speed, the US federal government response. He’s a partner with Medicxi Capital, and a former head of GSK’s vaccines division.

Mike Varney is stepping down from one of biopharma’s most scientifically influential jobs as head of Genentech Research and Early Development (gRED). He’s leaving at the end of July. He’s being replaced by Aviv Regev, a faculty star at the Broad Institute, and a leader of the Human Cell Atlas. (See Dr. Regev’s comments for a December 2019 TR article on the emergence of single-cell sequencing).  

Atul Gawande, the celebrated surgeon and author, stepped down from his role as CEO of Haven, the Amazon-JPMorgan-Berkshire Hathaway backed company. He said he plans to focus more on COVID-19.

Cambridge, Mass.-based Celsius Therapeutics, a company leveraging single-cell sequencing techniques for the treatment of cancer and autoimmunity, hired Jeanne Magram as chief scientific officer. She replaces Christoph Lengauer, a partner at Third Rock Ventures who co-founded the company, and who will remain as an advisor and board member to the startup. Rene Russo, CEO of Xilio Therapeutics, also agreed to join the Celsius board.

Waltham, Mass.-based AMAG Pharmaceuticals cut 30 percent of its workforce, or 140 workers.

Financings

  • Cambridge, Mass.-based QurAlis raised $42 million in a Series A financing to advance R&D against amyotrophic lateral sclerosis and other neurodegenerative diseases.
  • Cambridge, Mass.-based Dyno Therapeutics came out of stealth mode, generally describing its work on novel capsids that are supposed to improve AAV viral vectors, especially for delivery in ophthalmic, muscle, central nervous system, and liver disease. The company raised $9 million from Polaris Partners and CRV in 2018.
  • Palo Alto, Calif.-based Kriya Therapeutics raised $80.5 million in a Series A financing to develop gene therapies.
  • South San Francisco-based Sutro Biopharma, the developer of protein drugs in a cell-free manufacturing system, raised $98 million in a stock offering of 12.6 million shares at $7.75 apiece.
  • San Rafael, Calif.-based BioMarin Pharmaceutical raised $550 million in a convertible debt offering.
  • Newark, Calif.-based Protagonist Therapeutics raised $98 million in a stock offering of 7 million shares at $14 apiece.
  • Quest Diagnostics raised $550 million in a debt offering.
  • Cambridge, Mass.-based Axcella raised $52.3 million in a stock offering.
  • Cambridge, Mass.-based Akebia Therapeutics, a developer of drugs for kidney disease, raised $132 million in a stock offering of 11 million shares at $12 apiece.
  • Gaithersburg, Maryland-based Novavax said it stands to collect as much as $388 million from CEPI to develop its COVID19 vaccine candidate.
  • Menlo Park, Calif.-based Frazier Healthcare Partners said it put $15 million into a Series A financing for Lengo Therapeutics, a precision oncology company. Mike Gallatin, Roger Ulrich, Jim Bristol and Bruce Roth are all involved, working with partners in India.
  • New York-based Stellar Health, a health tech company, raised $10 million in a Series A led by Point72 Ventures.

Deals

Cambridge, Mass.-based Bluebird Bio and its partner, Bristol-Myers Squibb, were dealt a whopper of a setback at the FDA. The regulatory action said it can’t yet begin to review the application submitted to review ide-cel (bb2121), a BCMA-directed CAR-T immunotherapy for patients with multiple myeloma. The agency said more detail is required in the chemistry, manufacturing and control section of the application – and it can’t begin a formal review of the application until that work is done.

That’s a screw-up. The same day it announced this unforced error, Bluebird announced that it had renegotiated its partnership. BMS agreed to pay $200 million now so it doesn’t have to pay Bluebird milestones and royalties in the future on sales generated outside the US for both ide-cel and a second-generation BCMA-directed cell therapy. The companies will continue to split sales equally in the US. Bluebird stock traded as high as $63.55 the day before the announcement, and closed May 14 at $54.06.

Boehringer Ingelheim agreed to acquire Northern Biologics, a developer of drugs aimed at the tumor microenvironment. Terms weren’t disclosed.

Kirkland, Wash.-based Prevencio agreed to work with Seattle Children’s Research Institute to repurpose the Prevencio blood testing platform to detect signs of Kawasaki syndrome, a rare and very dangerous inflammatory reaction similar to the kind of inflammation seen in children with SARS-CoV-2 infections.

Data That Mattered

Brisbane, Calif.-based Myokardia said it hit all primary and secondary endpoints in a Phase III study of its mavacamten treatment for hypertrophic cardiomyopathy. The company issued a standard top-line press release with statistically significant p-values, showing the favorable result was not the result of chance. Like many companies in this enviable spot, MyoKardia held back the more meaningful details on the magnitude of clinical benefit seen in patients on the drug compared with the placebo. That will come later at a medical meeting, the company said. Immediately after announcing success, MyoKardia cashed in on the momentum in its stock price. It raised $551 million by selling 5.25 million new shares at $105 apiece on May 12. Shareholders won’t mind the minor dilution, as shares rocketed from $61.09 prior to the announcement all the way to $118 on May 14.

Regulatory Action

AstraZeneca and Merck won FDA clearance to market the PARP inhibitor olaparib (Lynparza) as a maintenance therapy for patients with advanced ovarian cancer, in combination with Roche/Genentech’s VEGF inhibitor bevacizumab (Avastin). The approval is for patients with homologous recombination deficiency, an umbrella term that includes patients with a BRCA gene deletion, suspected BRCA gene mutation, or genomic instability. The drug was found to extend survival by a median of 20 months in combo with the VEGF inhibitor, compared with the VEGF inhibitor alone.

Eli Lilly won FDA approval for selpercatinib (Retevmo) for patients with lung and thyroid cancers driven by RET gene mutations or fusions. This is one of the drugs Lilly obtained through its $8 billion acquisition of Loxo Oncology.

Abbott Laboratories won an FDA Emergency Use Authorization of a new COVID19 antibody blood test that runs on its Alinity i System. It has 99.6 percent specificity and 100 percent sensitivity, the company said. The new test is part of Abbott’s plan to ship 30 million antibody tests worldwide in May.

RUCDR Infinite Biologics, a bioprocessing lab affiliated with Rutgers University, won FDA clearance for the first saliva-based at-home test to detect SARS-CoV-2 infections. The test was developed in collaboration with Spectrum Solutions and Accurate Diagnostic Labs.

Quidel won FDA Emergency Use Authorization for a SARS-CoV-2 antigen test that can be run in 15 minutes. It detects active infection in samples collected from nasopharyngeal swabs, like the existing PT-PCR tests. It’s not as accurate as RT-PCR tests, but can be performed in point-of-care settings that have Quidel’s benchtop Sofia 2 analyzer.

Tweetworthy

13
May
2020

Coronavirus Vaccine Strategy: Larry Corey on The Long Run

Today’s guest on The Long Run is Larry Corey.

Larry is one of the nation’s best-known virologists and vaccine developers. Much of his research over the years has been on HIV, herpes simplex viruses, and viruses associated with cancer.

Larry Corey, MD; President and Director Emeritus; Member,
Vaccine and Infectious Disease Division, Fred Hutch; Principal Investigator, HIV Vaccine Trials Network

He’s the founding director and principal investigator of the HIV Vaccine Trials Network – a collaborative group to study vaccine candidates at 30 sites around the world. He’s based in Seattle at the Fred Hutchinson Cancer Research Center. He served as president and director of that institution in the early 2010s, but now is back to running his own virology lab.

Larry has spent 50 years thinking hard about viruses and how to combat them, dating back to a stint at the CDC during the Vietnam War days. Early in his career at Burroughs-Wellcome, working with future Nobel laureate Dr. Gertrude Elion, he developed acyclovir as the first effective therapy for genital herpes. As director of the AIDS Clinical Trials Group, he led the organization that proved combination antiretroviral treatments could control HIV. The team later demonstrated that these drugs could reduce transmission of HIV from mothers to their infants.

This whole set of experiences has shown him what each major player in the scientific enterprise brings to the table – academia, government, and industry.

All of this makes him a great person to talk to now about vaccine strategy for COVID-19. Just before we recorded this episode May 12, he published a perspective piece in Science with Tony Fauci, John Mascola and Francis Collins of the NIH. They wrote about how to think about spinning up an unprecedented global vaccine effort against the pandemic. See that strategy paper here.

This is a timely and frank conversation about one of the most important aspects of the pandemic response.

Please join me and Larry Corey on The Long Run.

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13
May
2020

If Trikafta Isn’t Good Enough for ICER, What Drug Is?

JessicaSagers, PhD; head of engagement, RA Capital

Last week ICER released a report concluding that Vertex’s groundbreaking triple-combination cystic fibrosis (CF) drug, Trikafta, is too expensive for the value it provides to patients.

By all scientific and clinical standards—including ICER’s own—Trikafta, a novel combination of a CFTR potentiator and two correctors, is a transformative drug. It compensates for a mutation present in 90% of all CF patients, turning a disease that has long been a death sentence into a manageable chronic condition. Following stellar Phase 3 data, the FDA approved Trikafta five months ahead of schedule. The patient, physician, and research communities exploded in exuberance when it was approved. NIH director Francis Collins, who helped discover the CFTR gene in 1989, whipped out his guitar and sang on stage in celebration.

ICER awarded Trikafta an “A” – its highest grade – for “certainty that Trikafta provides a substantial net health benefit over standard of care.” However, the magnitude of this achievement did not translate to a favorable review on price. Trikafta is priced comparably to similar drugs for rare conditions, at just under $24,000 per month in the US. And that’s a list price – insurance plans and Medicaid pay a lower but undisclosed net price, so after typical discounts and rebates (~15%), Trikafta’s net price is likely closer to $20,000 per month.

Once a patient starts on the drug, they have to stay on it to manage their disease. That’s not unusual for small molecule drugs or injectable biologics. But Trikafta works better for CF than most drugs work for their respective rare diseases. Even so, in ICER’s words: “Despite [Vertex’s CF drugs] being transformative therapies, the prices set by the manufacturer – costing many millions of dollars over the lifetime of an average patient – are out of proportion to their substantial benefits.”

This assessment caused an outcry among patients and foundations. They argued that the drug is a life-changer, and that ICER’s analysis didn’t include important variables that matter to patients. In a sentence that shocked CF families, ICER argued that even if Trikafta were able to generate a total functional cure such that patients never experienced any complications related to their disease, the drug would still not be worth paying for at the price set by Vertex:

“As an extreme scenario analysis, we evaluated Trikafta as a curative therapy and found that the cost-effectiveness ratio of lifetime therapy with Trikafta continued to far exceed commonly used cost-effectiveness thresholds even under the assumption that it maintained individuals with CF in normal health such that they never experienced any symptoms or complications of CF.” (emphasis added)

The callousness of this response aside, it isn’t that a drug—or even a cure—can never be overpriced. That’s conceivable, especially in the absence of any competition. But ICER tries to make the point that Trikafta is overpriced while leaving a lot of math on the table that does not suit its argument.

It’s worth exploring those overlooked variables and the societal norms that underlie value-based pricing analyses, which CF patients have cited in their defense of this vital medicine. It’s especially important to take this broader view considering how those norms might change following the COVID-19 pandemic. Let’s explore more accurate ways to model cost-effectiveness so that we don’t risk talking ourselves out of inventing what we really need.

Drug costs are mortgages, not rents

Healthcare costs in the United States are on the rise and will continue to increase. This is because paying for the time and expertise of trained medical professionals, keeping hospitals and clinics clean and operational, and maintaining the huge administrative burden of our medical system is expensive and will remain so. These costs are like an ever-rising rent that we as a society will always have to pay.

But drug costs are mortgages, not rents. Drugs are the only element of the healthcare system that not only pay for themselves but save our system money in the long run. How? They go generic. After a new drug enjoys a finite branded period, patents expire, competitors enter the market, prices drop by 85-90%, and that advancement belongs to society as a low-priced generic forever. By law, Trikafta will go this route one day, too, most likely within about 15 years from its launch, as nearly all small-molecule drugs do. Vertex’s monopoly is temporary, not permanent, by design.

But ICER’s methodology does not take into account the fact that any drug will go generic. Instead, they model the drug’s launch price as its price each year for the entire lifespan of each patient, wildly overestimating its total lifetime cost. 

For the sake of argument, let’s assume an average CF patient starts taking Trikafta at age 10 and gets the patented drug for 15 years. If the patient remains in steady health, as would reasonably be assumed based on the drug’s profile, that 25-year-old patient in the year 2035 can expect many more years of healthy living on this drug at a less expensive generic price, not today’s premium branded one. ICER isn’t unaware of this flaw; rather, they expressly refuse to address it.

When called out on this point multiple times by CF patients and foundations, ICER punts:

“As is consistent with best practices at international HTA agencies and with the great preponderance of academic work in health economics, ICER’s cost-effectiveness analyses do not routinely make estimates of price changes across comparator treatments linked to patent and exclusivity time horizons, especially given the unpredictability of these changes in the US health care market.”

Yet the fact that a small molecule drug like Trikafta will go generic is one of the few predictable things about healthcare. One can model the possibility that some patent gamesmanship may result in a few years’ delay of a generic launch (inappropriate though it may be), but when modeling value on the scale of decades, these uncertainties hardly alter the fact that Trikafta’s genericization is inevitable. ICER argues that uncertainty in the timing of genericization and whether the price will drop by 80%, 85%, or 90% precludes modeling it at all. This is a disingenuous strategy, to say the least, and ignores a simple modeling assumption that can and should be factored in.

Economists who have modeled the impact of genericization have pointed out that doing so reveals a drug to be two- to three-fold more cost-effective than misrepresenting its mortgage cost as rent. Payers, regulators, and the biotech community should spurn ICER’s analyses if they continue to neglect drugs’ core value proposition. At this point, continuing to refuse to account for genericization is tantamount to perpetuating disinformation.

COVID-19 expands our definition of value

What would it be worth to you to know that if you contracted COVID-19, there would be a safe, effective treatment to get you back on your feet?

What would that peace of mind do for you when deciding whether to allow family members to go back to work or school?

What would such reassurance do for the global economy?

The COVID-19 pandemic illustrates that another vital benefit that drugs provide (and value-based pricing analyses fail to capture) is peace of mind: the freedom to act, plan, and work without the threat of a disease hijacking your life.

The mother of a CF patient captures this intangible benefit in her exchange with ICER:

CF Mother: ICER’s report fundamentally fails to capture the monumental progress my son has achieved thanks to this triple-combination therapy. Increased pulmonary function is important, but it is the freedom to prepare for a fruitful future rather than to prepare for death that matters most. The larger point here is that the improvements that matter most to patients are not at the center of ICER’s cost-effectiveness analysis.

ICER: We modeled Trikafta as a cure and it still did not meet societal norms for cost relative to benefit.

What ICER dismisses is that “societal norms for cost relative to benefit” are ours to set. ICER’s “societal norms” reflect the norms of its own staff, and certainly the publicly stated sensibilities of its major backer, billionaire John Arnold. But they do not represent those of the majority of Americans, who view healthcare as a human right. America excels in nurturing the kind of innovation that advances its goals. It is within our country’s means and abilities to improve our health and that of the world.

With the capabilities of biomedical innovation now on display and the world calling for more COVID-19 investment from all of society’s pockets – government, insurance, non-profit, and private sector – the pockets that everyone acknowledges we must not reach into are those of patients. Patients need affordable drugs, and America can make that possible not just for most, as it does now, but for all with proper insurance reform. That means ensuring that all Americans are insured and minimizing barriers to access for essential medications (i.e. by reducing out-of-pocket costs). Then we can collectively incentivize and fuel innovation to solve our unmet needs. We can do that by paying branded prices that, while seemingly high per patient, are finite and, in the long run, represent better value than continuing to suffer from the diseases that plague us.

Right now in the US, because of Trikafta, about 30,000 patients have a new, hopeful outlook on life. Every one of them is surrounded by family members that can now worry less about managing the disease and start thinking more about pursuing their own dreams. There is substantial human potential that can be unleashed whenever a powerful new drug like Trikafta comes along. 

Until we achieve insurance reform for everyone, we can put some patches in place to pay for this advance. The COVID-19 pandemic has already shown us that this is doable: for example, by capping insulin copayments at $35 for everyone regardless of insurance status and offering many medicines for low fixed costs to tens of millions of the uninsured. If drugmakers and insurers can do this for patients now, they can do it in the future.

It’s time we recognize that value can’t be captured by a single organization’s formula – especially one with the gall to insist a launch price lasts forever and that disregards the value of curing a devastating disease for ourselves and future generations. It’s hard to think of a societal norm more American than investing towards an accomplishment as immense as conquering CF, taking pride as a nation in getting the job done, and celebrating the heroes who did it. 

RA Capital is a registered investment adviser. This material is not intended, and should not be construed as, investment advice or recommendation to invest in any security. Likewise, this material is not intended as a solicitation to invest in any RA Capital product or service.

11
May
2020

Science in Plain English for the Pandemic

Art Krieg is one of the leaders in the field of oligonucleotide drug discovery, going back to the 1980s. Today, he’s the founder and chief scientific officer of Cambridge, Mass.-based Checkmate Pharmaceuticals, a cancer immunotherapy company.

Art Krieg, founder and chief scientific officer, Checkmate Pharmaceuticals

It’s his job to explain scientific concepts to a variety of professional audiences. But he leveraged that skill recently to do an interesting thing — a plain English, yet highly sophisticated 14-minute webinar aimed at general non-scientific audiences. It’s for the Oligonucleotide Therapeutics Society, a group he co-founded and recently served as president.

In the video (below), Art distills some basics on RNA and DNA medicines and vaccines. He talks about why this is an exciting time, and how this new biology could be applied in the pandemic. He uses plain English, not jargon. His tone toward the audience is one of respect. He immediately answers the ‘why should I care?’ question in his first breath — these oligo drugs are saving lives. He’s optimistic, yet he doesn’t overhype.

Essentially, he’s doing what many scientific entrepreneurs are capable of — telling an interesting, balanced scientific story that people can understand and appreciate. I think this is something other entrepreneurs could do, so I asked Art a few questions below to provide some background color.

 

Timmerman Report: You’re a scientist, not a practicing clinician. Communicating technical material to lay audiences isn’t really part of your day job.

Art Krieg: True now, but before I went full-time into biotech, I had 19 years of patient care experience, and that has an indelible impact on the way you think. You learn the importance of patient education and communication: patients are far more likely to take a medication as directed if their doctor explains it in a way that they can understand, and so I tried to do that. During my NIH fellowship in rheumatology I became involved with patient education at the Lupus Foundation of America, which gave me a chance to try to explain new scientific advances to a larger population than I could reach as an individual clinician.

TR: If we think about it, each of us can leverage our skills in different ways to be helpful now. You’ve given lots of scientific presentations and have that skill. But had it been directed in this public-education way previously?

AK: When I was a young assistant professor at the University of Iowa, I enjoyed getting involved with the state Lupus Foundation, and giving talks on lupus research and therapy to local chapters. As time went on, I became more involved in professional organizations, co-founding the Oligonucleotide Therapeutics Society (OTS) as a way to try to help advance the development of this whole new class of drugs. 

TR: Was this public education webinar something you had been meaning to do for OTS for a while, but never got around to?

AK: At the OTS we actually had scheduled a meeting for just a few weeks ago with FDA, NIH academic centers, patients, patient organizations, and bioethicists around how to accelerate the development of oligonucleotide therapeutics for N-of-1 diseases, that are so rare that no company can afford to develop a drug, even though the existing technology can be used to potentially save some patients’ lives. Then the pandemic hit, and we decided to reschedule that meeting. My OTS colleagues suggested to me that instead, I should prepare a video for the public on how our technologies can be used against the coronavirus. The idea immediately appealed to me.

TR: How much time and effort did you put into this little labor of love?

AK: It ended up taking WAY more time than I expected – I think every night for a week or so and most of two weekends.  

TR: Did you get some help along the way?   

AK: I got a lot of helpful feedback from OTS colleagues, friends, and family on 4 different versions of the webinar, and it was quite painful because I had to really simplify the message enormously, and cut it down from more than half an hour in the first version to under 14 minutes in the final one.

TR: Why did you want to do this?

AK: These drug development technologies are incredible, and I really believe at least some of them are going to work in a time frame that matters – I really wanted to communicate that to people because I thought the lay public might be glad to know the great progress in developing drugs to stop the pandemic.

After I finished the webinar, I read that a quarter of all Americans would refuse to get a vaccine against SARS-CoV-2, even if it was FDA approved as safe and effective. That horrified me – people are going to die unnecessarily if they refuse these new vaccines, and some who refuse to be vaccinated will transmit the disease to others who will die. No vaccine is going to be 100% effective, and so we should expect that the elderly population who are most vulnerable will have a lower response rate to these new vaccines, just as they have with older ones.

I get it that many people are afraid of things that they don’t understand, and if that is what is driving this refusal to get a SARS vaccine, then I hope that by explaining how these new RNA and DNA vaccines work, perhaps some of those people will understand and change their minds. I hope to change people’s minds by explaining that these RNA and DNA vaccines are assembled from natural building blocks that are already present in our bodies, and that these vaccines harness the same natural immune pathways (through TLRs) that our immune system uses every year to fight off the many viruses around us.

I don’t think it’s enough for us in the biotech industry to “only” develop lifesaving technologies to create new drugs faster than ever before – if we want to realize the full impact that these drugs and vaccines can have in saving lives, then we also have to explain them to people in a way that they can understand, so that they can get comfortable with them. 

The aluminum salts (alum) in older generations of vaccines are safe, but the fact that alum is not a natural part of our bodies scares many people. Call me naïve, but in the case of these new vaccine technologies that use these natural pathways, I just cannot see how someone could understand how they work, and still decide to refuse them. If just a few people who would have refused the vaccine decide to accept it because of my video, then it will have been worthwhile. And maybe I can encourage other people to pick up this work, and to spread this message better than I can.

TR: What’s your biggest hope with this – maybe that the video gets circulated with high school science teachers?

AK: I would be delighted if high school teachers watch this, and spread it to their students! And I would be even more thrilled if some of those students somewhere in the world then get interested in science and oligonucleotide therapeutics, and come into this field and help us develop new generations of technologies for the future! 

7
May
2020

Keeping the Faith and Bracing for the Long Slog

Luke Timmerman, founder & editor, Timmerman Report

We’re suffering from a social disease. It ranks up there with COVID-19.

It’s boundless cynicism.

We need to tamp this down. Just like we need to wrestle the new coronavirus to the ground.

I’m not willing to accept “shit happens” as the national motto. This is a country of can-do problem-solvers. We can do so much better.

You can see the frightening level of callousness and self-centeredness, running like toxic rivers through our communications central nervous system.

First it was “oh it’s just old people dying.”

Then it was “oh, it’s just prisoners dying.”

Then it was “oh, it’s just some low-wage workers in meat-packing plants.”

Then it was “oh, it’s only 76,000 dead, and 2,000 more dead per day. It could have been worse.” Shit happens. Nothing you do about it.

Who cares?

I do. I care about people suffering and dying. I care about millions of people being out of work. We can reduce the toll of death and suffering while we also carefully re-open the economy. We can walk and chew gum. We have to. A long-term national lockdown can’t be sustained.

We have incredible capacity for problem solving. The United States of America is loaded with wealth and creative brainpower and people of good faith. We have talented women and men working day and night. In academia. In industry. In our state and local governments. And yes, across the federal government – at agencies like NIH, CDC, FDA, and the DOD.

People of good faith need to double-down in our efforts to combat the viral pandemic. And to combat the helplessness and carelessness fostered by this cynicism. Especially at this tense time, as antsy citizens everywhere start mixing and mingling while the virus is still spreading.

It will be a long, hard slog. There’s no doubt what it will take. Testing and tracing at scale. Well-designed randomized drug trials. A handful of bets on a portfolio of vaccine candidates. All of us wearing masks and limiting social contacts for longer than we’d like. Being kind and patient and empathetic.

We shouldn’t delude ourselves that this problem will magically fade away in August like one prominent model seems to predict. We shouldn’t tell ourselves that a Big Hairy Audacious Goal of a vaccine by end of 2020 or early 2021 is some kind of realistic expectation.

It will be immensely hard. It will take stamina. There will be setbacks. While this work carries on, we’ll have to tolerate the merchants of bad faith and their legions of followers doubting every one. We will have to turn the other cheek from time to time, as Internet and TV provocateurs traffic in the cynicism that butters their bread, and enables them to drown out the voices of reason. People will be encouraged, and tempted, to throw up their hands in despair.

We will not let the bastards get us down. We will remain steady and focused.

We will all need an occasional pick-me-up along the way.

This week, I’m leaving you with a couple things to lift your spirits.

One is the 1989 hit “I Won’t Back Down.” Watch Tom Petty belt out this anthem for steely entrepreneurs everywhere, and chuckle at the hair (which may be coming back into style, at least for this editor whose last haircut was in early January).

The other is the 1993 ESPY award speech by former North Carolina State University basketball coach Jim Valvano. He was dying from cancer. He said: “Don’t Give Up.”

Now, on to the highlights of the week in biotech.

Science

  • Modeling Shield Immunity to Reduce Spread, in Tandem with Social Distancing. Nature. May 7. (Joshua Weitz et al)
  • Immunology of COVID-19. Current State of the Science. Cell / Immunity. Mt. Sinai School of Medicine team. Sinai Immunology Review Project (Nicolas Vabret et al)
  • Autopsy Findings and Venous Thromboembolisms in COVID19 Patients. Annals of Internal Medicine. May 6. (Dominic Wichmann et al)
  • Pathological Inflammation in Patients With COVID19. Key Role for Monocytes and Macrophages. Nature. May 6. (Miriam Merad and Jerome Martin)
  • Factors Associated With COVID-Related Hospital Death Gleaned From Electronic Health Records from 17 Million People in the UK National Health Service. MedRxiv. May 6. (Ben Goldacre et al). Expanded statement from OpenSafely Committee.
  • SARS-CoV-2 Infection in the Placenta. MedRxiv. May 7. (Hillary Hosier et al at Yale)

Science News and Features

  • Beware Overblown Stories About Dangerous Coronavirus Mutations. The Atlantic. May 6. (Ed Yong)
  • Profile of a Killer. The Complex Biology Powering the Pandemic. Nature. May 4. (David Cyranoski)
  • Labs Across US Join Federal Initiative to Study Coronavirus Genome. NYT. Apr. 30. (Sheri Fink)
  • The Real Reason to Wear a Mask. The Atlantic. Apr. 22. (Zeynep Tufekci et al)
  • Coronavirus Hijacks the Body from Head to Toes. WSJ. May 7. (Betsy McKay and Daniela Hernandez)

Epidemiology

  • What Happens to Kids? NIH sponsors study to assess how many kids get COVID19. May 4. (NIH release)
  • Three Potential Future Scenarios. Recurring Small Outbreaks, a Monster Wave, or Persistent Crisis. STAT. May 1. (Sharon Begley)
  • What the Proponents of Natural Herd Immunity Don’t Say. NYT. May 1. (Carl Bergstrom & Natalie Dean)
  • Study Finds Nearly Everyone Who Recovers Makes SARS-CoV-2 Antibodies. May. 7. NIH Director Blog. (Francis Collins)

Humanity

  • Medical Students Need to Learn About Health Disparities to Combat Future Pandemics. AAMC. Apr. 30. (Selwyn Vickers)
  • Once Upon a Time, the Hero Sheltered in Place. New England Journal of Medicine. May 6. (Lisa Rosenbaum)

Access

  • Doctors Lambaste Federal Process for Distributing Remdesivir. STAT. May 6. (Eric Boodman and Casey Ross)
  • How Does the Government Decide Who Gets Remdesivir? Doctors Have No Idea. CNN. May 7. (Arman Azad)
  • Gilead Says It’s In Discussions With Manufacturers to Make Remdesivir Available and Affordable in Europe, Asia and Developing Countries Through At Least 2022. May 5. (Gilead statement).

Policy & Politics

  • The Economy Will Not Open Up Without a Credible Plan for Public Health. Medium. Apr. 7. (Andy Slavitt)
  • Trump Changed the GOP. He Didn’t Change America. Washington Post. May 7. (Jennifer Rubin)
  • COVID-19 in Rural America. Kaiser Family Foundation. Apr. 30. (Rachel Fehr et al)
  • Open States. Lots of Guns. America Is Paying A High Price for Freedom. NYT. May 5. (Charlie Warzel)
  • Show Evidence that Apps for Contact Tracing Are Secure and Effective. Apr. 30. (Nature editorial)
  • Polls Show Partisan Divide on the Pandemic. Axios. May 5. (Margaret Talev)
  • Asia’s Lesson for Tackling Coronavirus. Act Fast. WSJ. May 7. (Timothy Martin and Natasha Khan)

Investigations

  • Full Whistleblower Complaint from Law Firm Representing Former BARDA Head Rick Bright. May 5. Narrative starts on Page 27.
  • Vaccine Expert Says He Was Punished for Raising Concerns about Trump Administration Coronavirus Response and Nepotism. STAT. May 5. (Nicholas Florko)
  • Theranos Would be Thriving in the Pandemic. Medium. May 1. (Tyler Shultz)

Communication

TR Coverage of the Week

Treatments

Cambridge, Mass.-based Evelo Biosciences, with Rutgers University and Robert Wood Johnson Hospital in New Jersey, started up a Phase II trial of Evelo’s oral therapy for patients hospitalized with COVID19. The Evelo drug candidate, EDP1815, is a “monoclonal microbial” that has shown an ability to suppress production of multiple inflammatory cytokines – IL-6, IL-8, TNF, IL-1beta — that can spin out of control into dangerous cytokine storms. The drug showed that effect in a previous Phase Ib psoriasis study and in preclinical models. There’s a real therapeutic rationale, given the observation that many severely ill COVID19 patients suffer from  cytokine storms. Take that rationale, combined with a randomized, placebo-controlled study design, moving at pandemic speed, and you have a model for how things ought to be done. Data on safety and efficacy are expected in the second half of 2020. (Disclosure: Evelo CEO Simba Gill was on my Kilimanjaro Climb to Fight Cancer team last summer in Tanzania. I did a little fist pump for him and his team when I saw this trial).

Testing

Adaptive Biotechnologies announced a plan to start a 1,000-participant study called ImmuneRACE, which will look at antibodies to develop more fine-tuned diagnostics for COVID-19. The company, developer of an immune sequencing platform, is supported by its big cloud computing and analysis partner, Microsoft, and LabCorp of America, which will handle collection of blood and nose/throat swab samples that patients can take without having to leave home. (Read Adaptive CEO Chad Robins explanation of the study, and his thoughts on managing in this hard time on TR).

Deals

Moderna, the mRNA vaccine and therapeutics company, struck a deal with Lonza, the contract biologics manufacturer, to manufacture as much as 1 billion doses of its mRNA vaccine candidate. That’s a big number of doses, which everyone wants to see in a pandemic. But you have to read the release. It assumes the lower dose being tested now in a brand-new Phase II trial – a 2-shot prime-boost regimen of 50 micrograms, 28 days apart — will be the dose that provides a sufficient immune response. The other dose being tested in Phase II is 250 micrograms. Clearly, if that’s necessary, something will have to happen to boost manufacturing capacity to get to 1 billion doses.

VIR Biotechnology and Alnylam Pharmaceuticals said, after just three months of specific collaboration on RNA interference drug discovery for COVID19, that they’ve nominated a lead candidate for clinical trials, scheduled to begin around year-end 2020. Of the 350 candidates synthesized by Alnylam, multiple candidates were shown to deliver a three-log (three orders of magnitude) reduction in viral replication in a live virus assay in the petri dish experiments conducted by VIR. The lead candidate is being made into an inhalable formulation to get good distribution into the lungs.

Alexion Pharmaceuticals agreed to pay $1.3 billion in cash, $18 a share, to acquire Portola Pharmaceuticals, the hematology drug developer.

Magenta Therapeutics and AVROBIO, a couple of development-stage biotech companies in the Boston cluster, struck an unusual innovative smallco + innovative smallco partnership (as opposed to the usual innovative smallco + rich largeco deal). In this case, Magenta brings its antibody-drug conjugate to the table to enhance the conditioning of AVROBIO’s lentiviral gene therapies. Both of these companies have their roots in the Atlas Venture portfolio, so the players know each other well enough to entertain this sort of unusual alliance.  

New York-based Stemline Therapeutics agreed to be acquired by Italy-based Menarini for total consideration of up to $677 million.

South Plainfield, NJ-based PTC Therapeutics agreed to acquire Censa Therapeutics, the developer of treatments for orphan metabolic diseases such as phenylketonuria (PKU). PTC is paying $10 million cash upfront and 850,000 shares of PTC stock (market value: $46.91 a share on Thursday), plus potentially $217 million in milestones.

Eli Lilly agreed to work with Shanghai-based Junshi Biosciences to develop neutralizing antibody therapies against SARS-CoV-2.

San Rafael, Calif.-based BioMarin Pharmaceutical struck a partnership with DiNAQOR to develop gene therapies for rare cardiomyopathies.

Financings

Waltham, Mass. and Montreal-based Ventus Therapeutics secured a $60 million Series A financing led by Versant Ventures and joined by GV. Cash will be used to advance three pipeline programs based on structural immunology insights on how to make small molecules versus hard targets of the innate immune system.

Cambridge, Mass.-based Praxis Precision Medicine announced its debut with $100 million in financing from inception, led by founding investor Blackstone Life Sciences. It’s working on rare brain diseases.

Grail, the early cancer detection company in Menlo Park, Calif., raised $390 million in a Series D financing. That’s a lot of money. It’s also a lot less than the company raised in prior venture rounds. See TR coverage from Grail’s founding in January 2016.

Bridgewater, NJ-based Insmed fetched $259 million in a public offering of 11 million shares at $23.25 apiece.

Redwood City, Calif.-based Pulmonx raised $66 million to further develop its minimally invasive valve for treatment of severe emphysema. Ally Bridge Group led.

Lyra Therapeutics raised $56 million in an IPO at $16 a share to advance its ear-nose-throat programs. Sorry, I missed this one from Apr. 30.

Vapotherm, an Exeter, NH-based med tech company focused on respiratory distress, raised $87.5 million through a public offering of 3.35 million shares at $26.

Carlsbad, Calif.-based GenMark Diagnostics raised $70 million in an offering of 7.2 million shares at $9.65 apiece.

San Diego-based Kura Oncology raised $125 million in a stock offering of 9.1 million shares at $13.75.

Sunnyvale, Calif.-based Silk Road Medical, a company working on stroke risk reduction, raised $75 million in a stock offering.

Personnel File

Alex Aravanis, the co-founder and chief scientific officer at Grail, is returning to Illumina to be the chief technology officer at the DNA sequencing market leader. Mostafa Ronaghi, the longtime CTO at Illumina, will move over to a new role as SVP of Entrepreneurial Development at Illumina. Ronaghi also joined the board of Grail, which spun out from Illumina four years ago to work on early detection of cancer.

Brian Di Donato was hired as chief financial officer and head of strategy for Immunocore, the UK-based company developing T-cell receptor therapies for cancer. He was previously CFO at Achillion Pharmaceuticals.

Stephen Webster joined the board of TCR2 Therapeutics, a cancer immunotherapy company working on T-cell engineering. He’s the former CFO of Spark Therapeutics.

New York-based Lodo Therapeutics hired Donald Marvin as chief financial officer.

Seattle-based Impel Neuropharma said that chairman Adrian Adams will be taking over day-to-day leadership as chairman and CEO, effective immediately, and that previous CEO Jon Congleton will be leaving the company.

Sutrovax named Andrew Guggenhime as chief financial and chief business officer.

New York-based Schrodinger, a computational drug discovery company, named Jeffrey Chodakewitz and Gary Ginsberg to its board of directors.

Burlingame, Calif.-based ALX Oncology named Rekha Hemrajani to its board of directors.

Data That Mattered

Regeneron Pharmaceuticals and Sanofi said the PD-1 inhibitor cemiplimab (Libtayo) passed a pivotal study of patients getting their second round of therapy with locally advanced basal cell carcinoma.

Roche offered a preview of presentations it plans to release at the ASCO virtual meeting in late May, including results from a Phase II study of tiragolumab, Roche’s novel cancer immunotherapy designed to bind to TIGIT, being tested in combo with its PD-L1 inhibitor for non-small lung cancer.

Cambridge, Mass.-based Akebia Therapeutics said it passed the first of two Phase III clinical trials with its vadadustat, an experimental treatment for anemia in patients on kidney dialysis.

Regulatory Action

Gilead Sciences, on May 1, secured an FDA Emergency Use Authorization for remdesivir, the first antiviral treatment for hospitalized COVID-19 patients. The company said it would donate all its supplies to the US government, which will now handle distribution to hospitals. Days later, regulators in Japan cleared the drug for use there. See FDA Fact Sheet for patients and caregivers.

Roche won FDA Emergency Use Authorization for a serology test (antibody test) with an impressive 99.8 percent specificity rate and 100 percent sensitivity rate. The healthcare giant said it would provide “high double-digit millions of tests” per month, starting in May. These are the kind of tests that will be crucial to give people confidence to go back out and about as countries around the world have to gradually lift their physical-distancing restrictions.

The FDA, after being accused of foot-dragging on approvals of PCR diagnostic tests in the early days of the pandemic, was accused of going into a dangerously laissez faire Wild West mode with the next round of tests – serology tests to assess antibody production against the virus. On May 4, the agency pumped the brakes, ordering manufacturers of antibody tests that lack data to cough up data on test accuracy in the next 10 days or else get yanked off the market.

AstraZeneca won FDA clearance for dapagliflozin (Farxiga) to reduce the cardiovascular death and hospitalization in patients with heart failure. This approval opens up a large new patient population for this oral, once-daily SGLT2 inhibitor. The drug was originally developed for Type 2 diabetes and continues to be marketed for that indication as well.  

Novartis got the FDA green light to start marketing its MET inhibitor, capmatinib (Tabrecta) metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to MET exon 14 skipping (METex14). Foundation Medicine provides the FDA-approved companion diagnostic to identify the 4,000-5,000 patients in the US who are thought to be good candidates for this drug.

Cambridge, Mass.-based Sherlock Biosciences won an FDA Emergency Use Authorization for a simplified CRISPR-based diagnostic test for COVID-19. The company’s scientific co-founders include Feng Zhang of the Broad Institute, David Walt at Mass General Hospital (founder of Illumina), and Jim Collins of MIT. The hope is this will be a quick and cheap test that will allow for testing capacity to increase. (See NYT coverage by Carl Zimmer). Further scientific background at STOPCovid.

Johnson & Johnson and Genmab won FDA clearance for daratumumab hyaluronidase-fihj (Darzalex Faspro) as a new subcutaneous injectable form of the drug for multiple myeloma.

Tweetworthy

Much is being said about a spirit of collaboration in industry. That’s good. What’s better are hard and fast and lasting changes to the way clinical trials are done. See comments by Andy Plump of Takeda. h/t Pearl Freier.

Worth a Watch

NIH Director Francis Collins, in his inimitable and lovably nerdy way, plays this adapted tribute song to frontline healthcare workers in the COVID19 pandemic, to the tune of “Imagine” by John Lennon. Watch this for 4 minutes and it will brighten your day.

7
May
2020

Randomized Controlled Trials For Healthcare Delivery Work; Now Let’s Do More At Scale

David Shaywitz

The value of randomized controlled trials (RCTs) in healthcare delivery was highlighted earlier this year with the publication in the New England Journal of Medicine (NEJM) of a paper that rigorously evaluated a deeply appealing hypothesis: that you can improve care and reduce costs by focusing on “superutilizers” – the patients who consume the most healthcare resources. 

I discussed this paper, and some associated issues, at a recent Harvard Department of Biomedical Informatics (DBMI) faculty journal club, and thought a few highlights might be of particular interest to TR readers.

The story of the trial is captured magnificently by the Tradeoffs podcast – you can listen here, and read a helpful summary here

The protagonist is a New Jersey physician named Jeffrey Brenner, who became interested in better serving patients in Camden, New Jersey. It’s a city with 74,000 people across from Philadelphia. About 42 percent of the population is African-American, and about 37 percent of the population lives in poverty, according to the US Census Bureau. After reviewing hospital data, Brenner realized that hospital use, and more generally, healthcare costs, weren’t evenly distributed. 

In this population, like others, a small percentage of patients (about 5%) accounted for the vast majority of healthcare costs (~ 50%). This group of people has been dubbed the “5/50’s.” Many of these “superutilizers” are patients facing a remarkably complex group of social and economic challenges that can make life, and health, disproportionately difficult for them. 

Brenner’s hypothesis was that a key challenge these patients face is engaging effectively with the healthcare system, and by providing them with a team of guides (sort of like sherpas), to help coordinate their care, the patients’ health would improve, and hospital utilization would decline. Initial work seemed to bear this out – healthcare costs and utilization seemed to go down for the first several dozen patients treated in this program.

It all seemed to make a lot of logical sense.

Brenner’s star really began to rise after his efforts were profiled by Atul Gawande in an inspirational New Yorker article, “The Hot Spotters,” in 2011; Brenner received a MacArthur genius award in 2013, and his program was widely hailed as a success, which many sought to emulate.

Yet Brenner, it turns out, encountered skeptics at health conferences. To his exceptional credit, he recognized the need to further test his hypothesis, and really pressure-test his program, through a randomized control study.

This trial was led by an independent, trusted group from MIT, led by noted economist Amy Finkelstein. Brenner himself left to join United Healthcare Group in 2017, attracted, he said, by the opportunity to apply some of his learnings from an even larger platform – that of the world’s largest insurer.

The MIT results, published in the NEJM in January 2020, were disappointing. There was no difference between control and treatment arms in the number of hospital readmissions within 180 days – the primary endpoint.  Moreover, both groups showed a decline in utilization, suggesting that the previously-observed decrease seen in the first group of patients may well have represented simply an example of the well-described phenomenon of “regression to the mean.”

There are several relevant lessons we might learn here.

First, the study highlights that even – perhaps especially – when there’s a compelling narrative, it’s critically important to perform the rigorous study to be sure that what you might so desperately want to believe is actually true. There are so many ways we can fool ourselves, and so many potential confounders; RCTs – while not without their own issues, in particular, generalizability – help minimize the effect of bias, which is why they’re appropriately considered the gold standard.

The value of randomized controlled trials (RCTs) is perhaps most acutely felt in situations where the truth feels self-evident, to the point where actually doing a study can strike some as unethical. 

Prominent examples from the history of medicine are the use of an anti-arrhythmia drug to reduce sudden cardiac death after heart attacks (the intervention seemed intuitive, yet the CAST study revealed the drug actually made things worse); the routine use of pulmonary artery catheterization in critically ill patients (collecting more data intuitively seemed better, yet RCTs revealed no evidence for improvement; a wag even penned an obituary for the device); and perhaps most famously, the use of hematopoietic stem cell transplant for the treatment of breast cancer (the trial was derided by some as unethical given the assumed benefit, yet the approach was found not to improve survival significantly).

The need for careful study is particularly important, and particularly challenging, in areas characterized by what tech entrepreneur Jim Manzi (Tech Tonics interview here; TR discussion in context of AI here) has called high “causal density.”

This is a term referring to “the number and complexity of potential causes to the outcome of interest.” It’s a factor in biological experiments, of course, and an even greater factor, Manzi argues, in areas of social science. If a vaccine works in one population, he says, he’s reasonably confident it will work in another. But if an educational intervention works in one setting, he’s far less confident it will be generalizable, because of all the factors that could be involved.

Perhaps not surprisingly, when many policy measures are actually evaluated by RCTs, most fail.  A study from Arnold Ventures revealed that of “13 instances in which the federal government commissioned large randomized controlled trials to evaluate the effectiveness of entire, Congressionally-authorized federal programs,” 11 essentially failed, one yielded modest/marginal benefit, and only one clearly and repeatedly seemed to work: the Department of Defense’s Guard Youth ChalleNGe, intensive, residential youth development program for high school dropouts.

A frustratingly common observation is that initially promising data often fail to stand up to the test of time.  As I discussed in a recent Wall Street Journal review of their book, The Power of Experiments, Harvard Business School professors Michael Luca and Max Bazerman share the story of a thoughtful behavioral intervention developed by University of Pennsylvania faculty Katherine Milkman and Angela Duckworth.  While initial results looked promising, the effects soon receded – prompting Duckworth (of Grit fame) to observe, “Behavior changes are really *#$@ing hard!”

Yet all may not be lost.

In 2014, a White House Social and Behavioral Sciences Team (SBST) tried to reduce the over-prescription of addictive medicines (Schedule II controlled substances) by sending out a letter informing these doctors they prescribed far more of these medicines than their peers; this type of approach (as I discussed in the Journal) was demonstrably successful in another context — increasing delinquent tax payments, for example. 

Yet here, a RCT evaluating this approach failed to demonstrate an impact on prescriptions.

Instead of giving up, however, the team refined their approach, modifying both the targeting of their letter (now focusing on primary care doctors who were unusually heavy prescribers of quetiapine [Seroquel], specifically) and the language used (in addition to peer comparison, the letter noted the doctor was under review by the Centers for Medicare & Medicaid Services [CMS]), and performed another RCT.  This time, it seems, the approach worked well; prescribing was reduced by over 11%, a statistically significant effect that persisted for at least two years.

According to experts like Manzi, success in environments of high causal density require just this sort of iterative approach. 

“Run enough tests,” he advises, “and you can find predictive rules that are sufficiently nuanced to be of practical use in the very complex environment of real-world human decision making.” 

Testing at this scale, Manzi says, requires “integration with operational data systems and standardization of test design,” approaches that are already adopted by a number of organizations within the business world. 

Examples, as I discussed in the Journal, include not just tech giants like Google, Microsoft, and Amazon, but also companies like Nike and State Farm, the insurance company. I’ve also discussed the value of “high velocity incrementalism” to use Harvard Business School Professor Stefan Thomke’s term, in TR, here, and in the context of COVID, here.

Strikingly, “run enough tests” turns out to be the advice of Amy Finkelstein, the MIT economist leading the Camden RCT, as well. In an April 2020 Perspective piece in the NEJM, Finkelstein argued that the key to improving healthcare delivery was conducting more RCTs, noting “the increased availability and use of administrative data have made implementing RCTs easier and less expensive than it once was.”

She noted that improved data systems (versus what were available two decades prior) capturing hospital discharge data enabled the Camden RCT study to be done “at substantially lower cost and effort and with less risk of nonresponsive bias” that would have been possible in an era that relied upon survey data collection.

Finkelstein added that “administrative data also enable use of RCTs for low-cost, rapid testing of repeatedly fine-tuned interventions,” citing a 2019 NEJM study from NYU Langone Health, led by my med school colleague Leora Horwitz, reporting the completion of “ten randomized, rapid-cycle quality-improvement projects in one year.”

We’ve seen the ability of deliberate experimentation at scale to impact website traffic and hone the appeal of political messages to voters. 

How exciting to contemplate the integrated — and, I hope, routine — use of this process to improve the delivery of care to patients.

6
May
2020

Extending an Immune Medicine Platform Against the Common Foe

Chad Robins, co-founder and CEO, Adaptive Biotechnologies

Every few days, I walk through our labs to say hello to my colleagues. They are the ones who are literally and figuratively keeping the lights on at Adaptive Biotechnologies.

Rest assured, I’m maintaining physical distance while seeking human connection. With a Telepresence Robot that I can drive with a remote control from my home, I’m able to get real-time updates on the day-to-day work being done, and hear how employees are doing. It’s a high-tech version of “management by walking around.”

As Adaptive’s CEO and co-founder, it is a top priority for me to stay socially connected with all of our employees while we are mostly isolated. Especially our lab and lab support staff. Executives like me have meetings on Zoom with partners, investors, and my executive team. People in the labs are the ones coming into the office every day, taking extra safety precautions.

They are making sure our important work on behalf of our patients continues to move forward.

This has been a hard pill to swallow. I seriously want to be there in person. We’ve been keeping our distance for two months now. But we must continue to protect our essential lab employees by staying home.

We are all in unchartered waters. While COVID-19 may be bad for our physical health, it also has the potential to threaten our mental health and well-being, especially as the pandemic drags on. Like many others in the biotech community, I am grateful to be healthy and productive while so many others have not been as lucky. And like so many around the world who continue to shelter in place, I get what this new normal means. Home schooling my two teenage daughters, virtual birthday celebrations with family, and online all-company meetings – it’s not the same, but it’s amazing what we can continue to do all of this with technology.

At Adaptive, we are fortunate to be able to contribute. Our immune sequencing platform gives us a powerful tool that can be used both for quantitative molecular diagnostics, and, potentially to identify neutralizing antibodies to be made as therapeutics against the SARS-CoV-2 virus.

We are working harder than ever to deliver on this urgent need. We sometimes feel gratitude, but also the stress that comes with a demanding job, homeschooling, isolation and blurry lines between work and personal time. When, exactly, should you take a break? This is new to us all, and we’re all doing the best we can.

Extending the Company

Our story with COVID-19 starts in late February when we saw the early warning signs in other countries but just before the virus brought the U.S. to its knees. Adaptive president Julie Rubinstein came to my brother and co-founder, Harlan, and I with a persuasive proposal: we already had the technology to help advance solutions for this virus. It was time to jump in.

I reached out to our long-time partner Microsoft, and Peter Lee immediately agreed to lock arms on this endeavor. We originally partnered in 2018 to create the TCR-Antigen Map, an approach to map population-wide adaptive immune responses to diseases at scale with a simple blood test.

We’ve been looking at diseases where there’s no single biomarker of inflammation to look for. We can see a broader immune repertoire at work, which is necessary for understanding a more complex and nuanced immune response that you see in many diseases. Since the beginning of our partnership, we have confirmed clinical signals in two diseases, and established our first proof of concept in molecular diagnosis of Lyme disease.

Given the maturing state of our technology, we knew we could potentially help on both the diagnostic and therapeutic front against COVID-19.

Our lead independent board director, Peter Neupert, happens to also be the lead independent director of LabCorp of America – one of the two biggest diagnostic companies in the US. Peter helped make the connection to quickly bring LabCorp into the fold with us. Illumina, the DNA sequencing leader, and Providence St. Joseph, a major healthcare system on the West Coast, then joined forces with us. By Mar. 20, we announced a joint effort to find the relevant immune response signature to the virus to help advance solutions.

We all agreed to do what isn’t normally done in industry — to make the data available to any researcher, public health official or organization around the world via an open data access portal.

Since then, new information about the virus and potential solutions continue to mount with remarkable speed. The first US death was reported on Feb. 29. Now, on May 6, Covid-19 has claimed more than 72,000 lives in the US. We are learning that the virus may be far more widespread than originally thought.

There are many unanswered questions with the current RT-PCR testing paradigm.

  • Can it detect asymptomatic carriers?
  • How about segment patients based on immune response of those who will develop mild symptoms versus those who will require hospitalization?
  • Can it tell us which patients have truly cleared the disease?

We hope to answer one, if not many, of these questions with one test.  

Right now, to contain the spread of COVID-19, the world needs more of the existing tests, and other kinds of tests.

A new virtual clinical study, ImmuneRACE, sponsored by Adaptive and Microsoft, will enroll 1,000 participants around the US. We’re seeking to map and measure the immune response to COVID-19 to inform a cellular immune test to potentially help address current challenges in testing. As part of the study, we will measure the presence of T cells, which identify the disease early and multiply to combat the infection.

In parallel, we expanded our partnership with Amgen to develop potential antibody therapies for COVID-19. Like others, we think that neutralizing antibodies may be effective since this virus seems to mutate more slowly than other RNA viruses and mutated strains are genetically similar – making them likely susceptible to a broadly neutralizing antibody in the months ahead. The promise of an approach using engineered neutralizing antibody therapies is the ability to select and confirm the best antibodies and manufacture them in large quantities. Amgen is a world leader in engineering and manufacturing antibodies. This was a perfect pairing of our immune sequencing platform with the world’s largest biotechnology company.

We have seen some early successes using convalescent plasma therapy to boost the ability of patients with severe cases of COVID-19 to fight off the infection, but this approach is not sustainable in mass quantities. Our goal is to find the strongest antibodies from patients who are actively fighting or have recovered, and manufacture them into a therapeutic that can be used in two ways: for treating patients fighting the disease, and to prevent the disease in those at higher risk, such as healthcare workers. 

We see ourselves as well-positioned to respond. Our technology can read the immune system, which is different from other solutions which focus on the virus itself. That means we can let the immune system tell us which are the strongest antibodies to neutralize the virus without assuming what those antibodies are targeting. We also have the scale and speed to assess a much broader pool of possible antibodies against a wider range of targets. Our platform allows us to look at all the activated antibodies in patients currently fighting the virus. We aren’t limited in our view to just 1-2. We then funnel them down through a series of techniques to find the best antibodies. This may also dictate whether we develop a single antibody therapy or a cocktail of antibodies, and at what point during treatment an antibody therapy would have the greatest impact. It’s like being able to scout every high school basketball player at the same time — Michael Jordan, Scottie Pippen, LeBron James – to assemble a Dream Team of antibodies.

We are all racing to find solutions, and we will need many to address the magnitude of this problem. I’ve been privileged to be one of the voices representing the diagnostics perspective as part of several national working groups. It has been amazing to see such an unprecedented level of collaboration. Normally partnerships with big companies like Microsoft and Amgen, or with academic research centers, would take months to years to materialize. Instead, we moved in days and weeks, acting on “virtual” handshakes. 

We all know there is no time to lose, and you see this reflected across the entire industry.

I wish I had the foresight to know now what lessons I will learn as this plays out. For now, I’ll share two thoughts. The first is sincerity – be sincere. I want my employees to know that I care about them, that I worry about them, that I am thankful to them for showing up every day. That human connection is something that cannot be replaced by technology.

My other advice: we all have a role to play in ending this pandemic, whether it’s working in a lab, serving food, or staying home. People are dying. If you are in a position to help, in whatever way you can, you have an obligation to humankind. Sometimes people find purpose in surprising and remarkably generous ways, like the people who are delivering restaurant meals to testing labs in my hometown of Seattle. That helps both the lab workers, and the restaurants. There are things we can call do.

It is my biggest hope that we – our whole community – can make an impact, together.

5
May
2020

Giving Models and Modelers a Bad Name

Ruth Etzioni, Full Member, Division of Public Health Sciences, Fred Hutch Cancer Center

As someone who has spent a career building and studying disease models, primarily for cancer, the latest update from Chris Murray and the IHME model makes me cringe.

The IHME model, readers will recall, has been frequently cited by the White House coronavirus task force. On May 4, the IHME called a press conference to release the results of their COVID-19 model update which showed a staggering departure from their prior predictions of about 60,000 deaths through the end of August.

Obviously, this earlier model had to be updated – and  fast: the official US death toll was already at more than 68,000 at the time of the May 4 press conference.

The new prediction from IHME through August estimates 134,000 deaths – more than double the previous model’s estimate. Murray, the institute’s director, told reporters that the death toll was significantly increased because the latest update had taken changes in mobility into account. Indeed, travel patterns now show an uptick in movement in states that are beginning the re-opening process, and increased mobility means increased opportunity for infection.

Murray, in a May 4 interview on CNN with Anderson Cooper, said the earlier model was built on an assumption of statewide social distancing measures remaining in effect through May in order to suppress transmission. Now that states are lifting the orders, the model had to be revised to incorporate the fact that “more people are getting out and about.” 

While I am in total agreement that premature relaxation of social distancing will lead to an explosion of new cases and deaths, you don’t need a model to know that. That’s how epidemics work when a population is as far away as the US is from herd immunity. And models everywhere are showing the same thing.

Where I live in Washington State, Gov. Jay Inslee and his advisors looked at models that predicted dramatic growth of infections if the state were to relax the Stay Home, Stay Healthy order prematurely. Those models were part of the rationale for extending the stay-home order until the end of May.

It makes a nice story, to tell the world that the reason your model’s predictions have changed is because the population’s behavior has changed. The implication is that it’s not the model’s fault, it’s the politicians and the people’s shifting behavior. Indeed, that was the same explanation given by IHME for their model revising its early death toll of about 90,000 dramatically downward to about 60,000 in early April. At that time, Murray explained that the change in predictions showed that social distancing had been a wild success – better than we could ever have imagined.

The lowering of the death estimate, in turn, led to howls of protest that we had over-reacted by shutting down and staying home. Those howls put pressure on elected officials to relax social distancing. Clearly, models do matter.

On Apr. 14, I wrote in these pages that that the interpretation regarding social distancing success was wrong and misleading and placed far too much credibility in the early predictions. The early model results were based on an oversimplified empirical model. It extrapolated death curves from the earlier experience in China, Italy, and eventually Spain. It assumed that social distancing would work as well as in those settings, and that the pattern of deaths after the peak would be a mirror image of the pattern before it. Revisions of the model tried to soften these assumptions, making many other assumptions along the way. It is likely that these revisions, rather than social distancing success, drove the dive in the deaths predicted in that April revision.  

The same thing is happening now. A quick skim of the IHME’s model updated site leads one to an eye-glazing list of changes, including some that have nothing to do with mobility and everything to do with improving how well the model matches the data on cases and deaths recorded up until this point.

When Murray spoke about mobility patterns causing an update to the model, he neglected to say in the same breath that the team had made fundamental changes to its model-building approach in order to arrive at its current set of predictions. IHME is now more like a hybrid of empirical and mechanistic approaches. What we aren’t seeing from IHME is a clear and transparent statement on the truly humbling “back to the drawing board” nature of what it has just done by rebuilding its model.

Here is one change that truly raised my eyebrows: 

“Since our initial release, we have increased the number of multi-Gaussian distribution weights that inform our death model’s predictions for epidemic peaks and downward trends. As of today’s release, we are including 29 elements… this expansion now allows for longer epidemic peaks and tails, such that daily COVID-19 deaths are not predicted to fall as steeply as in previous releases.”

This change alters the shape of the assumed mortality curve so it does not go down as fast; it alone could explain a substantial portion of the inflation in the revised mortality predictions. 

The proof is in the Washington State pudding. The IHME is no longer predicting that we will have less than one case per million on May 28 and can therefore safely reopen, as it did in its previous incarnation. But little has changed here on the policy front and in residents’ mobility patterns, according to Google Mobility reports, through April.  

I am not aiming my comments at the IHME modeling team, which I imagine is sincerely doing its best to deliver results that match the data and produce ever-more-complex predictions of the future. They are working overtime to fit the rapidly evolving and imperfect data, marching to a drumbeat of deadlines from everyone that wants the impossible – crystal clear and precisely accurate forecasts. To their credit, the last part of the May 4 update does note that both model changes and increased mobility projections could account for the change in predictions. But that never made it into the headlines. And that is a problem of transparency.

Transparency begins in the sincere effort by those who communicate models to make sure that they are properly interpreted by the policymakers and public that are using them. The IHME pays lip service to transparency by documenting their model’s updates on their website. But their pages-long description is chock full of technical fine print and is hard to understand, even for a seasoned modeler like myself.

A key part of transparency is acknowledging your model’s limitations and uncertainties. This is never front and center in the IHME’s updates. It needs to be.

It is ironic to me that I am being this critical when I agree so strongly with the message that is being broadcast as a result of this update. Make no mistake – if some states that are opening prematurely, or some that are considering doing so, change their minds as a result of this update, it will a very good thing. 

We have to remember that this epidemic took root and grew massively in every state from miniscule beginnings. We should all be sobered by our real-time experience of exponential growth. If there is an ambient prevalence of more than a handful of cases in any state, then anything that increases the potential for transmission will lead to a re-growth. We do not need a model to be able to predict that. But, as we plan for how to reopen in each state of our union, we need to know what extent of growth in new infections we can manage. And models can help us with that. 

When and how much we can reopen will depend on the surveillance and containment infrastructure that we put in place to control upticks and outbreaks. I am convinced that models can help us think clearly about complex policy questions – such as finding the balance between changes that increase transmission and measures to contain it. Models, along with other data and evidence, can guide us towards making sensible policy decisions. I have seen this happen time and time again in my work advising national cancer screening policy panels.

But as modelers, we have a responsibility. We have to be humble. We must make sure that the key caveats and uncertainties that are the nature of our work find their way into the headlines and are not relegated to the fine print.

If we don’t, we will give modeling, and modelers everywhere, a bad name.

5
May
2020

The Spirit of Giving Is More Powerful Than Ever

Kelly O’Brien, VP of philanthropy, Fred Hutchinson Cancer Research Center. (Illustration by Praveen Tipirneni)

When people look back on the pandemic, they will be amazed by the outpouring of generosity.

The response from frontline healthcare workers, scientists, and the biopharmaceutical industry is simply extraordinary. Food banks and social services are also saving lives.

The common thread is the inherently human capacity to be generous.

The word philanthropy brings to mind a variety of images, from PTA bake sales to benefactors whose names appear on buildings. With Greek roots meaning “love of mankind”, philanthropy today is defined more broadly as using one’s time, talent, or treasure to improve the human condition.

I come from the generation that went trick-or-treating with UNICEF coin boxes, and have worked as a professional fundraiser for more than thirty years. I have one of the best jobs in the world raising money for one of the world’s leading scientific organizations, Fred Hutchinson Cancer Research Center.

More than $425 billion was given to all kinds of good causes in 2018 in the US alone. In June, GivingUSA will release its annual study for calendar year 2019 and it’s likely that we will see some increase. Whatever the number, private donations represent, on average, 2% of our GDP per year. That level of giving is pretty consistent, year after year. It may not sound like a lot as a percentage of the economy, but these numbers capture only a fraction of our annual generosity.

Beyond our borders, philanthropy is also increasing. While there is no comprehensive data source, the Charities Aid Foundation tracks charitable behaviors in 146 countries. Developing nations often report the highest responses for “helping a stranger” and “volunteering.”

Historically, disasters evoke a desire to help, with more than 40% of Americans saying that they have given in response to earthquakes, hurricanes, and tsunamis. We started the year with a global outpouring of support for those suffering from the Australian wildfires. I am sure many of you gave. Tragic events, whether in our neighborhood or a continent away, ignite our desire to be helpful.

Now, donations in response to COVID-19 are increasing at a rate that rivals the spread of infection and, to borrow a catch-phrase—this is one curve we do NOT want to flatten.

The Center for Disaster Philanthropy estimates that more than $9 billion has already been committed to COVID-19 response, research, and relief efforts. I cheer every time I see news of a big gift. Really—I let out a little “woo-hoo” while working at my kitchen counter. Jack Ma, Bill and Melinda Gates, Jeff Bezos, Aliko Dangote, Lady Gaga, the Wellcome Trust, Google, Microsoft, Amazon, and many more are putting their resources and wealth to work around the globe. While some debate the merits and motivations of giving by the world’s wealthiest, I’d argue that this is no time for cynicism. Charitable giving is completely voluntary. I am grateful for any and all who give.

Here, civic leaders launched #AllinSeattle and raised nearly $30 million—from gifts of all sizes—to provide support for food instability, small businesses, homelessness, rent assistance, and children impacted by school closures. Our city is not alone in these efforts.

While big gifts make headlines, it’s everyday generosity that is the greater source of hope. Thanks to today’s tech, ways of giving have been transformed. You can swipe, tap, and transfer while staying home. I can “Ask Alexa” to donate for me. My Facebook feed presents fundraising options every time I post or peer into the lives of my friends. The social media platform has raised more than $3 billion from 45 million people since introducing this feature five years ago.  

At the same time, the lines between non-profit status and the ability to ask for donations is gone. Crowdfunding enables us to support projects as diverse as a teacher’s classroom, a friend of a friend’s hospital bill, an entrepreneur who needs to pay rent, or the Veronica Mars movie.

Here’s the best part. Philanthropy is about so much more than giving money. The challenges of COVID-19 have brought forth an equally unprecedented spirit of support.

We moved quickly to donate food for healthcare workers and to food banks. We’re making masks. We’re giving blood or plasma. We’re cleaning our closets and donating to shelters. Staying home makes each of us a philanthropist.

The creative community has sprung in to action with concerts and conversations. Ben Gibbard, Tim McGraw, Yo-Yo Ma, Debbie Allen, and John Krasinski are making physical distancing a little less socially isolating. Yoga classes have pay what you wish options. Our hair salons and favorite restaurants have GoFundMe accounts to help sustain their employees.

We have a long road ahead. At Fred Hutch, we are rethinking everything. We are visiting with donors through Zoom. We’re hosting virtual Town Hall conversations with our researchers to increase understanding on the pandemic. And we’re postponing or transforming our spring and summer fundraising events.

Many of you reading this are familiar with (and have donated to!) our Climb to Fight Cancer program. We also have a phenomenal bike ride, walk, and run event every August. Obliteride and dozens of other fundraising events are now being reimagined and recreated with physical distancing and stay-at-home guidelines as our top priority.

I had set a really big personal goal this year—riding 100 miles with 3,000 others members of the Fred Hutch community. With a virtual fundraising event, and way too much time in front of a screen these days, I will adjust. Maybe I’ll ride 25 miles four days in a row. Whatever I decide, we are not unique. Every organization you care about is simultaneously scrambling and innovating and counting on you.

Events serve many purposes, foremost being the empowerment of those participating. Fred Hutch’s volunteers and donors believe in the power of research to save lives. Whether it’s a 5k, a specially prepared meal and entertainment, or climbing 832 steps up the Space Needle, these events create shared purpose and community around a common goal. Traditionally, here, that goal is curing cancer. That’s still our focus. Fred Hutch also has four decades of expertise in studying infectious diseases and we have scientific studies underway to help forge a path forward for COVID-19.

Kelly O’Brien

This work is just one piece of the vast biomedical research enterprise. Our governments are pouring money in to medical and market solutions. The resources it will take to create a vaccine for billions of people—and to sustain our healthcare and public health systems—so that history doesn’t repeat itself is staggering. It’s almost hard to imagine.

When the time comes and we look back on what got us through, it will be our generosity.

 

Kelly O’Brien is Vice President for Philanthropy for Fred Hutchinson Cancer Research Center.

May 5th is #GivingTuesdayNow a global day of giving and emergency response to the unprecedented need caused by COVID-19.

Donate Now

 

 

4
May
2020

If We’re Smart, COVID19 Will Strengthen Our Defense Against Drug-Resistant Bugs

Vidya Atluri, MD PhD, infectious disease fellow, University of Washington Medical Center

The COVID-19 pandemic makes it clear that infectious diseases can devastate the world with remarkable speed. But long before this crisis, we were fighting another infectious scourge below most people’s radar – antimicrobial resistance.

One estimate by the CDC in 2013 found that 2 million people in the US get infected with drug-resistant bacteria, leading to a huge toll of suffering, death, and economic cost. These infections can strike anyone, any time, and the problem is global in scope. Bacterial infections like tuberculosis, pneumonia and salmonella are becoming harder to treat as these bugs and others evolve and evade our current arsenal of antibiotics.

Paul Pottinger, MD. Director of the Infectious Diseases & Tropical Medicine Clinic at University of Washington Medical Center; University of Washington professor of Medicine and Allergy and Infectious Diseases; Director of UWMC’s Antimicrobial Stewardship Program

Our main weapon in that fight: antibiotic stewardship, meaning the right drug for the right bug for the right duration. If we aren’t careful in how we use the antibiotics we currently have, we face the risk of drug-resistant bacterial infections that could leave another brutal mark on our society.

Although our resources are understandably diverted to rise to the challenge of coronavirus, the fight against antimicrobial resistance continues. COVID-19 presents many obstacles, but also opportunities.

If we as physician-scientists take the initiative, and proceed deliberately — not impulsively changing standard of care based on every anecdotal report — we will emerge with a stronger, more impactful public health system that responds to both viral pandemics and the long-neglected, emerging disaster of bacterial drug resistance.

The Right Bug

Antibiotics don’t treat viruses. This is basic knowledge for almost everyone at this point, not just physicians. And yet … the majority of viral respiratory infections are treated with antibiotics.

Why? Diagnostic uncertainty. How do clinicians know if an infection is viral … or bacterial … or bacterial after viral? Or … does this patient even have an infection at all?

Diagnostic uncertainty is the fundamental driver of inappropriate medical antibiotic use, aka overprescribing.

Long before COVID-19, the solution has been either giving antibiotics to patients at highest risk for complications or “watchful waiting.” That means avoiding antibiotics unless things get worse. Neither solution is ideal. And, neither should be acceptable.

The market has already responded with very reliable molecular testing for respiratory specimens. The technical performance of these assays is superb, and their turnaround time is short … and yet, their cost and regulatory concerns prevent them from being deployed in every medical office in the nation. Some insurance plans will cover this expense, but many will not … and only some offices are willing to take on the burden of ensuring they are CLIA-approved to perform these assays on-site.

If we are savvy, the pandemic will lead us to fix this problem. The massive buildup of a  network of point-of-care rapid testing platforms could be leveraged for use against SARS-CoV-2, but also for other respiratory infections long after this pandemic is gone. In this case, this federal investment could pay off in unseen ways for decades to come.

The other exciting development that shows promise is self-administered at-home viral respiratory testing. It has performed spectacularly here in the Pacific Northwest (initially through the Seattle Flu Study, now retooled against COVID19 under the new name of SCAN).

Using the nation’s rapid parcel delivery infrastructure to get specimens to reference labs is no longer a pipe dream. Everyone knows Amazon can get a package to your doorstep in a day. The general public intuitively gets that they can take advantage of this capability by taking a sample at home and shipping it to a lab. The urgency to do this kind of testing is clear. In the near term, our goal must be to diagnose COVID-19 correctly right away, because these patients are at high risk for getting antibiotics they may or may not need … which will further exacerbate our systemic pre-existing problem of breeding antimicrobial resistant (AMR) organisms.

On the other hand, the emphasis on COVID-19 within the community and healthcare settings leads to encounters focused on one question: “Does this patient have COVID-19?”

Answering that question, without going on to “What else might this patient have?” may lead to premature diagnostic closure. By focusing on COVID-19, we can miss our opportunity to treat other infections, from flu to strep throat. While most of those patients will recover on their own (hence the success of “watchful waiting”), some will go on to have complications, which may require longer durations of antibiotics than if the patient had been treated early on. The longer you have to take a course of antibiotics, the greater the opportunity for the bacteria to develop resistance to the drug.

The Right Drug

The response to COVID-19 has included the quest for an effective medical treatment. In some cases, we have proceeded thoughtfully by conducting well-designed, randomized, controlled trials. In other cases … not so much.

Time is a precious resource in a pandemic, and if physicians are acting too much in the moment based on the latest anecdotes or published case series or yesterday’s hunch, then they’re spending time that could be better used by enrolling patients in a well-designed clinical trial that could give us solid evidence to act on in a couple months.

Although our hunger to help is palpable—and very understandable—the rush to publish or espouse unproven claims might have very real adverse effects. As we have learned the hard way, time after time, the disciplined response often turns out in the end to be the best response. An oft-repeated mantra in antimicrobial stewardship is, “Don’t just do something… stand there!”

This is true whether we are considering treating a mild infection with antibiotics, even if we feel that treatment is unnecessary, or whether we are considering using an experimental agent in an unproven manner. In antibacterial drug stewardship, of course, the concern is that our injudicious use will accelerate resistance.

A similar concern relates to respiratory viral infections: During the 2009 H1N1 “swine flu” pandemic, the antiviral oseltamivir (marketed by Roche as Tamiflu) was used indiscriminately, and this was associated with genesis of drug-resistant influenza.

It is too soon to know whether COVID-19, another RNA respiratory pathogen, will develop resistance to treatments to come, although this question is very much on our minds now in light of the happy news that remdesivir is approved for administration to severely ill patients under an emergency use authorization.

Will this drug be used willy-nilly? We certainly hope not, and the EUA mechanism may help protect against that… for now. Time and again, out of our eagerness to help patients, we medical professionals have over-prescribed antibacterials, and that pattern may play out in the case of whatever treatments are (we hope) ultimately proven to help in COVID-19.

Overprescribing of an antiviral could have serious consequences. One of the strange features of COVID-19 is that treating a virus may have collateral damage in terms of increasing antibacterial resistance, if the antibiotic azithromycin is commonly prescribed in combination. To be clear: If randomized trials support its use, then we are all for that! Outside of trial use, we do have concern for this practice, not only for its potential to drive resistance but also because of possible cardiotoxic side effects.

The Right Surveillance

Antimicrobial stewards have long worried about the amplification of resistant bacteria in skilled nursing facilities, assisted living facilities, and long-term acute care centers. The patients tend to be elderly and infirm, with multiple co-morbidities, and frequently are treated for respiratory or urinary infections (probably too frequently).

Now, enter COVID-19, which has a strong predilection for this exact same patient population, often with lethal results. Surveillance testing of workers and residents of these facilities has revealed that some have a strikingly high prevalence of SARS-CoV-2 viral PCR test positivity, suggesting that this group remains at risk and may serve as a reservoir of infection for prolonged periods of time.

What if surveillance could be expanded to include multi-drug-resistant gastrointestinal or genitourinary colonization? It would only take a simple extra step of sample collection. Could the knowledge gain enhance infection control practices, and guide prescribers in their choice of antibiotics for those who need to be treated? Bringing surveillance to this at-risk population is an attractive opportunity.

The Right Tools

COVID-19 has ushered in telemedicine, with a vengeance. We applaud that. It’s about time! The desire to help patients avoid healthcare settings has led to an incredible increase in remote medical visits, potentially increasing access in underserved areas, especially rural areas far away from major hospitals.

The effect of remote visits on antibiotic prescribing is yet to be determined. Perhaps the ease with which these visits can occur will decrease the impulse to prescribe an antibiotic in order to make patients feel like they got something for their trouble of spending time driving to the clinic, sitting in traffic, finding a place to park, etc. On the other hand, the inability to truly examine the patient physically in person could increase antibiotic prescribing “just in case” the reported symptoms are being caused by some unknown bacteria. Better remote medicine capabilities could also enhance collaborations between healthcare workers in the farthest corners of the world – to help them make better choices, which will protect us all.

This epidemic has taught us that we are all connected, and microbes don’t respect boundaries of any kind. We need to cross boundaries even faster.

1
May
2020

A Time for Empathy

Luke Timmerman, founder & editor, Timmerman Report

This is a fragile moment.

It’s May 1. Some of us have been in social isolation for two solid months. Everyone’s at some point on the continuum of stir crazy. More than 30 million people are out of work. Tempers are flaring. Protestors are carrying guns. It’s obvious we can’t sustain a maximalist social-distancing policy much longer.

Today, we have half of the 50 states doing some kind of partial lifting of stay-home orders, some variations on gradual re-opening of their economies – even though only 14 states are reporting declines in new cases. Masks, regular deep cleaning, shift work, and physical spacing in normally crowded spaces are all being tried out to mitigate the spread.

This virus is so befuddling, it’s hard to say much of anything about it with certainty. But it seems safe to say that some places will be more successful than others at keeping infection rates down with a careful turning of the dial.

The curves are deeply disappointing. We’re in what looks like a long plateau of steady infection and death. We now have more than 1 million confirmed cases of COVID19, and more than 63,000 confirmed deaths. More than 2,000 people are dying per day.

Our failure to run adequate diagnostic testing leaves us flying blind, unable to execute on the classic test/trace/isolate strategy that everyone agrees is essential, and which South Korea and others have shown works.

We had the tiniest glimmer of encouraging news this week about an antiviral medicine, remdesivir. It was shown in a rigorous NIH-sponsored study to reduce hospitalization time by four days. It’s not much in the grand scheme of things. An improvement in survival rates would be a bigger deal. Still, the result counts for something, because it can relieve some pressure on hospitals.

Really good news, in the near-term, would be the US getting its act together on testing, tracing and isolation. If we do that, then it should be possible for as little as 7 percent or so of the population to be isolated at any one time, allowing the rest of us to go about our business. Betz Halloran, an outbreak modeler at Fred Hutch working with collaborators at Northeastern University, made that remark in a panel discussion I moderated for Life Science Washington a week ago.

How much work needs to be done to get to adequate testing? As of May 1, we have done 6.5 million tests in the US. Grand total since late January. A Harvard group says we need to do 5 million tests A DAY by early June, and 20 million A DAY by midsummer.

We have our work cut out in more ways than one. We can’t duck the testing issue, because vaccines or seriously good treatments in the form of neutralizing antibodies will almost certainly not magically appear before the second wave.

Which brings me to my final point.

Our society needs to take a look in the mirror about how we treat each other, because we’re going to be in this betwixt-and-between mode, with partial re-opening and partial re-tightening, for a while. It’s a psychological tension we will all have to manage for longer than any of us would like.

Pathological selfishness, cruelty, and callousness has been coursing through our information ecosystem for years. Bad faith has been ascendant. A 24/7 information war has been raging, driving millions of people to extreme views that were unthinkable not that long ago.

The virus has struck us at a dark time.

The infowar has depleted our society’s empathy reservoir. You see it in popular Internet memes, like “Boomer Remover.” You see a guy in the Michigan state capitol, taunting National Guardsmen by breathing in their face, as if to blow smoke from a cigarette. You do see acts of kindness and empathy and courage on the news, but they are offset by this ugly behavior. It’s like a stain on our soul.

This is a test for our society.

This moment reminds me of something passed down from my Dad. He was idealistic at first, and then disillusioned, like many Vietnam veterans. He didn’t want his son to enlist in the Army. And yet, he was deeply patriotic. He instilled that spirit in me. It’s still there with me every day. I believe in our institutions like NIH, CDC, FDA. In our universities. In our entrepreneurial spirit. In our form of democratic self-governance – of the people, by the people, for the people. In our Bill of Rights. In our checks and balances that protect us from monarchy and tyranny.

It’s painful to see people traffic in abject cynicism, thumbing their noses at CDC guidance, clamoring for hydroxychloroquine without evidence, and injecting bleach. The erosion of support for and belief in science — as the best rational means for understanding the world — is a devastating indictment of life in the 21st century.

Now we can see how this cynicism about our institutions and our fellow citizens compounds.

We see it in sharp relief in a pandemic that disproportionately harms the most vulnerable. The elderly. Veterans. Prisoners. Black and brown people who can’t flip the switch and work from home. Low-wage workers in meat-packing plants. Native Americans on reservations.

I remember another thing my Dad taught me.

“A society is judged by how it treats the most vulnerable,” he said.

This quote, or variations of it, have been attributed commonly to Fyodor Dostoevsky, to Mahatma Ghandi, and Harry Truman.

We should remember those wise words, and act on them as best we can.

If we can foster some more humanity toward our fellow citizens, we might just come out the other side of this in a more perfect union. If we can resist the urge to call people names, even when they do things like stick hair dryers up their noses or go to the grocery store without masks, we can begin the process of turning down the cruelty and viciousness and ignorance and extremism. There are plenty of other things to do. Donate to your local food bank. Send a kind letter to an old friend from the other side of the aisle.

We can’t swing a sledgehammer to eliminate the cruelty. We have to radiate kindness.

What are you doing every day to uplift people?

Now, on to the rest of the week in biotech.

The Big Data Readout

The NIH reported results from a randomized study of 1,063 hospitalized patients with COVID19 who got Gilead Sciences’ antiviral drug remdesivir or a placebo. The median time to recovery from illness was 11 days for patients on the drug, and 15 days on the placebo – a 31 percent improvement, which was statistically significant. The drug didn’t show a statistically significant benefit on survival rates, although there was a slight trend in the right direction. Tony Fauci, director of the National Institute of Allergy and Infectious Diseases, called it “quite good news” and the kind of data that will create a new standard of care.

Gilead Sciences separately reported that another study showed that a 5-day course of treatment was about as good as a 10-day course of treatment. That’s meaningful because it means Gilead will be able to treat more patients with whatever supplies it can manufacture.  

Worthwhile Reading From Around the Web

Testing

Vaccines

  • An Oxford Group Takes the Lead in Vaccine Race. NYT. Apr. 27. (David Kirkpatrick)
  • What You Need to Know About a Vaccine. Gates Notes. Apr. 30. (Bill Gates)

Science Features/Commentary

Science

Epidemiology

  • A Grim Milestone at 100 Days. From 1 case to 1 million. Medium. Apr. 30. (WA Dept of Health)
  • Almost half of US – 45 percent of the Population – Is At Increased Risk from COVID19 Because of Co-Morbidities. Centers for Disease Control and Prevention. Apr. 27. (Mary Adams et al)

Investigations

Policy

Communication

  • Journalism Is Under Attack from Coronavirus and the White House. But We’re Winning. NBC News. Apr. 27. (Andy Lack)

Worth a Listen

Non-Covid Science

Feasibility of Blood Testing, Combined with PET-CT, to Screen for Cancer and Guide Early Intervention. Science. Apr. 28. (Bert Vogelstein et al)

Data That Mattered

Regeneron and Sanofi reported a not-so-encouraging update on the IL-6 inhibitor, sarilumab (Kevzara). A Data Safety Monitoring Committee recommended a halt to enrollment in an ongoing Phase III of COVID-19 patients with “severe” disease, but recommended continuing enrollment of the cohort with “critical” disease. The companies will also quit giving the low dose, and give everyone the higher dose.

Regeneron and Sanofi had better news from a trial of their PD-1 inhibitor cemiplimab (Libtayo). The drug reduced the risk of death by 32.4 percent in a study, compared with chemotherapy, when evaluated in patients getting their first round of therapy for locally advanced or metastatic non-small cell lung cancer, and with greater than 50 percent of their tumor cells positive for the PD-L1 protein. The finding was so strikingly positive that a Data Safety Monitoring Committee recommended the study be halted early so all patients could get the drug. The companies said they will take the data to US and EU regulators in 2020.

Roche reported that orally administered liquid risdiplam, a survival motor neuron-2 (SMN2) splicing modifier, passed a Phase II clinical trial for infants ages 1 to 7 months with Type 1 spinal muscular atrophy. Researchers reported a significant increase in motor function after 12 months of therapy. If approved by regulators, it would be an alternative to Novartis’ Zolgensma gene therapy, and Biogen’s Spinraza. For this product, Roche leads clinical development, in collaboration with the SMA Foundation and PTC Therapeutics.

Financings

Cambridge, Mass.-based Rome Therapeutics raised $50 million in a Series A financing from GV, Arch Venture Partners and Partners Innovation Fund. The plan is to make drugs for cancer and autoimmunity based on knowledge of repeat sequences of DNA, aka “the repeatome.”

San Diego-based Erasca Therapeutics, a targeted cancer drug developer, raised $200 million in a Series B financing. Arch Venture Partners and Cormorant Asset Management co-led. Jonathan Lim, former CEO of Halozyme and Ignyta, is the co-founder and CEO.

Shanghai-based Mabwell Biotech raised $280 million in a Series A financing. It’s reportedly a rollup of nine R&D and production companies in China.

Oakland, Calif.-based Dascena, a machine learning for diagnostics company, said it raised $50 million in a Series B led by Frazier Healthcare Partners. The company also announced a publication in the BMJ of an algorithm it made to help doctors treat severe sepsis.

Seattle-based Avalyn Pharma raised $35.5 million in a Series B to continue work on pulmonary fibrosis and chronic lung allograft dysfunction. Norwest Venture Partners led. Bruce Montgomery is CEO.

Dallas-based Taysha Gene Therapies raised $30 million in a seed financing co-led by PBM Capital and a fund led by former AveXis CEO Sean Nolan. The company said it’s working on 15 AAV gene therapy programs.

Personnel File

Nathanael Gray and Priscilla Yang, star chemical biologists, are moving from the Harvard/Longwood Medical universe to Stanford University. See the fist pump below from Stanford’s Carolyn Bertozzi. (See was a guest on The Long Run in 2019).

Sue Desmond-Hellmann joined GV as an advisor. She’s the former CEO of the Bill & Melinda Gates Foundation, chancellor at UCSF, and president of product development at Genentech. See the fist pump below from GV partner David Schenkein, who worked with Sue at Genentech.  

New York-based Health Reveal, a clinical AI company, hired Julie Stern as chief technology officer.

Waltham, Mass.-based Xilio Therapeutics, a cancer immunotherapy company, hired Martin Huber as chief medical officer.

Rosana Kapeller was named CEO of Cambridge, Mass.-based Rome Therapeutics (see above). She’s the former chief scientific officer of Nimbus Therapeutics.

Deals

Vertex Pharmaceuticals struck a research collaboration with Waltham, Mass.-based Affinia Therapeutics to work on novel adeno-associated virus (AAV) capsids for gene therapy. Initial focus will be on Duchenne muscular dystrophy, myotonic dystrophy type 1 and cystic fibrosis. Affinia will get up to $80 million in upfront and milestone payments during the research term.

Just Evotec, a leading biologics manufacturer, agreed to work with Ology Bioservices on antibodies for coronavirus. Ology is supported by a defense contract, and is tapping Just as a subcontractor. Terms weren’t disclosed. (See Just Evotec EVP Jim Thomas, on scaling antibodies and vaccines for COVID-19, in this Apr. 16 editorial on TR).

UK-based AstraZeneca and the University of Oxford, also in the UK, announced plans to collaborate on a recombinant vaccine candidate for SARS-CoV-2. Academics bring the discovery work, while industry brings development, manufacturing and distribution capabilities to the table. The first Phase I trial started last week. Terms weren’t disclosed.

Catalent, a contract drug and biologics manufacturer, agreed to work with Johnson & Johnson on manufacturing scale up for the company’s lead COVID19 vaccine candidate. Catalent said it will hire 300 workers to do the job.

Regulatory Action

San Diego-based Neurocrine Biosciences won FDA clearance to market opicapone (Ongentys) as a once-daily oral pill in addition to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes.

GSK secured the FDA green light to start marketing its PARP inhibitor niraparib (Zejula) as monotherapy maintenance treatment for women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, regardless of biomarker status. This is one of those anticipated label expansions that GSK anticipated would make its acquisition of Tesaro pay off.

30
Apr
2020

Real-Time Tracking of Viral Outbreaks: Emma Hodcroft on The Long Run

Today’s guest on The Long Run is Emma Hodcroft.

Emma Hodcroft, molecular epidemiologist, University of Basel; co-developer, NextStrain.
Photo: Oliver Hochstrasser / www.oliverhochstrasser.ch

Emma is a molecular epidemiologist at the University of Basel, and the co-developer of Nextstrain.

NextStrain is the open-source toolkit built for real-time tracking of viral outbreaks. In the early days, teams led by Trevor Bedford at Fred Hutch and Richard Neher in Basel used it to track viral evolution of Ebola and Zika. Over time, the resource has been adapted to study flu, and now – of course — SARS-CoV-2.

Lots of questions remain about this virus. It’s brand new to science. But a fair bit of what we do know from the early days can be attributed to Nextstrain.

This resource provides real-time information on where community transmission of the virus is occurring, where certain variations are coming from, the estimated size and scope of the outbreak, and more.

It’s a treasure trove. The whole world is watching.

In this episode, Emma provides clear, simple explanations of the basics of viral family trees, what we can learn from them, and what kinds of things we hope to learn later this year.

The Long Run is sponsored by RareCyte.

RareCyte delivers Precision Biology products and services for circulating tumor cell and multiplex tissue analysis designed to accelerate your cancer research. RareCyte leverages a world-class assay design team and end-to-end platform with biomarker-enabling technology to provide CTC assays that are rigorously validated for accuracy and reproducibility.  

RareCyte is the only full-service provider delivering custom assay development services, long-term biobanking of patient samples, CLIA-validated CTC enumeration, multi-biomarker analysis, and single cell retrieval for DNA sequencing.

RareCyte products for comprehensive CTC analysis include the AccuCyte Sample Preparation System, RarePlex Staining Kits, and CyteFinder Instruments, all of which are easily deployed in research labs worldwide.

RareCyte currently supports a wide range of global clinical trials with deep expertise, personalized service, and short turn-around times. Keep your research on track by engaging the RareCyte services team at info@rarecyte.com or at rarecyte.com.

28
Apr
2020

Keeping an Academic Lab Afloat in a Pandemic

Jim Olson, member, clinical research division, Fred Hutch; pediatric oncologist, Seattle Children’s; professor, University of Washington

Two months ago, our lab at Fred Hutch was on a roll.

After six years of hard work building technology platforms to discover protein drugs — infrastructure that few academic labs have — we were beginning to reap the rewards. Our team had grown to 36 people. Morale was high. A slew of our papers were accepted to high-impact journals. Clinical trials based on our work led to significantly higher survival rates for two groups of high-risk pediatric brain tumor patients.

This is the kind of impact we dream of in pediatric oncology.

But we were just getting going. Our lab had just spun out a third biotech company. The other two, founded more than a decade ago, were still doing well and advancing in human clinical trials. I was sketching out plans to hire five new post-docs in the coming years with the intention of simply letting them take our platforms for a high-octane ride to see what diseases they could drug that have to date been undruggable.

Now, my primary goal is to keep the lab afloat with the existing team.  We are limited to how many people can be in the lab at the same time, to stay in compliance with physical distancing requirements.

While necessary to protect our workforce, their families and the larger community, these measures have interrupted business as usual for bench scientists. We’re mitigating this with creative lab schedules —  who wants the graveyard shift! — and working from home when possible. But there’s no sustainable replacement for consistently being at the bench, day after day, thinking about experiments, brainstorming with energetic colleagues in real-time.

As we transitioned to primarily working from home, some of the post-docs and staff scientists on the team were working to exhaustion. Day and night, they analyzed data, wrote manuscripts. The boundaries of ordinary life have dissolved. You don’t just pull an 18-hour day in the lab, and then blow off some steam at a local bar with a colleague. You’re home alone, and in many cases, the desire is there to just disappear in the work.

Work is always there, but academic lab teams have to wrestle with the same everyday concerns as everyone else. They need to take care of themselves emotionally, while also meeting family demands. Like how to do their work while also educating kids at home when school is out.

To counter the pressure of all these competing demands, we start each Zoom meeting with a chat about what team members are doing to care for themselves. For those with young kids, I remind them that family time is awesome, but they also need some mommy or daddy time. In peer sessions with other mentors, we’re learning how to show enthusiasm for group progress during this period without placing the burden of high expectations on individual team members.

As the principal investigator, it’s my job to make sure we have the funds to keep everyone working, and to deliver on our research agenda.

None of us privileged enough to run a lab gets even gets 10 minutes of business training. Yet there you are, personally responsible for keeping the lights on and securing the salaries, benefits, and research costs for those working in the lab. You have to figure it out. It’s always top-of-mind. You have got to constantly be on the prowl for new grants. You are competing with brilliant colleagues from all over the scientific community for a finite pool of funding – everyone wants and needs their own tiny slice of the NIH funding pie. That pie doesn’t automatically get bigger every year, and you don’t automatically get renewals when your research bears fruit. Only about one in seven grant applications succeeds. There are no guarantees.

Biotech companies are often a good source of collaboration, and sponsored research agreements can be mutually beneficial. But in a recession, they have their own budgets to worry about. In stressful times, they tend to limit outside spending, perhaps by reducing sponsored research collaborations with academics.

As for philanthropy, donors are feeling the squeeze. They are worrying about their portfolios from one day to the next. That’s not an ideal position of confidence from which to write big checks.

Which brings me back to the grant writing to the federal government. Our applications have to absolutely sing. Fail a little too often with grant applications, and you might have to find a new line of work.

Fortunately, I haven’t had to lay anyone off. But many labs will face a financial shortfall at exactly the time that our institutions are facing profound financial challenges. NIH and non-profit foundations that provide grants to support our work have demonstrated extraordinary flexibility during the altered work schedule. Some have offered to allow us to pay scientists off the grants they awarded us at the same salary levels as in previous months, even though many cannot conduct experiments. Some have shifted deadlines or offered no-cost extensions. Even with these accommodations, like so many in the world right now, academicians face the need to limit expenditures and increase revenue.

Individual investigators typically have only two levers to pull to increase revenue: write grants or secure sponsored research contracts with industry. The silver lining to sheltering at home seemed briefly to be, “Well, at least I’ll have time to write grants.” It turns out that pipe-dream swiftly turned into perpetual Zoom meetings during the day, a brief stretch of time in the evening for family, exercise, and dinner, followed by a groggy return to the computer at 9 or 10 pm to finally work on more grants. 

Seeing that writing a couple of disjointed paragraphs each day wasn’t going to cut it, I blocked time on my calendar for uninterrupted grant writing.

Then came the knocks on the door.

“Daddy, there’s a dead and bloated Pomeranian washed up on the shore of the lake. Can you help me get it and bring it to the vet for chip identification?”

How can I say no to quality family time like that? 

Balancing family, treating kids with cancer at Seattle Children’s Hospital, managing a 36-person lab, spinning out companies, writing grants and finding time for friends and exercise to stay physically healthy was challenging enough prior to the pandemic.

In this new era of extreme multi-tasking, I now close my eyes at the beginning of each yoga session and offer my intentions to the good health of Ruth Bader Ginsburg (as always) and to finding the grace to someday write a full page of my grant application.

Jim Olson is a Professor at Fred Hutch and the University of Washington and an Attending Physician at Seattle Children’s Hospital.  He is a co-founder of Presage Biosciences, Blaze Bioscience, and Link Immunotherapeutics.

28
Apr
2020

We Didn’t Become the World Biotech Leader By Sealing Ourselves Off

Bernat Olle, CEO, Vedanta Biosciences

In the last four years, the U.S. administration has committed an endless string of hostile and indecent acts toward immigrants.

There was the border wall pledge. The Muslim travel ban. Increased screening and tight limits on refugees seeking asylum from war-torn regions. Most insufferable of all, we all witnessed the horrifying conditions faced by children, taken from their families, and kept in border detention.

Last week, President Trump announced he will sign an executive order to close the United States to immigrants. This doesn’t refer to illegal immigrants, but to all immigrants, period.

This is the culmination of a long-term goal for this administration. For all the previous talk of cracking down on illegal immigration, the most debilitating anti-immigrant measure the administration had taken up to this point had been to shut down the flow of legal immigration. We see it in the biotech industry.

Immigrant visas are down 25 percent since 2016, according to the Washington Post. The American Immigration Lawyers Association says that visa processing delays have reached crisis levels under the Trump administration. In particular, the H-1B visa, which has always had much more demand than supply, has been squeezed.

Like me, an immigrant from Catalonia, the northeastern region of Spain, so many international students educated in U.S. universities have used the H-1B as the on-ramp to the American dream. Many local biotechs, including my company, rely on the H-1B to recruit the best employees from around the world to Massachusetts.

In the last two years, processing times for visas have increased by 50 percent, despite a decrease in applications. The percent of application approvals has also decreased.

Judging from last week’s announcement, it looks like the worst is yet to come.

Last December, which now seems like an eternity ago, I traveled with my son to see an FC Barcelona soccer game in Catalonia, where I grew up. I wanted my son to see the great Messi play at least once.

Why did Messi emigrate from Argentina when he was a young teen? Why do teenage rising stars grow up yearning to play for FC Barcelona and not their countries of birth? Because their childhood idols played there. Because it’s the Mecca of football. And because it’s an international city that welcomes people from around the world with open arms.

Every year, more than 1,000 kids try out for FC Barcelona’s youth academy. Between 1979 and 2009, just 440 kids went through the youth academy: half were local, the other half from the rest of the world. Only 40 made it to the first team.

This is the deceptively simple recipe for creating the best team in the world: be a magnet for the best global talent, mix it with homegrown talent, repeat. It raises the bar. The locals get better. An epicenter of excellence emerges. Everyone benefits.

This made me think of my adopted hometown. What makes people from all over the world want to come to Boston to work in biotech?

Boston is the Mecca of biotech. This is where Henri Termeer, from the Netherlands, built Genzyme. It’s where Biogen flourished after its founders Charles Weissmann (a Hungarian-born Swiss), Phil Sharp, and Wally Gilbert first started it in Geneva, Switzerland.

Boston is where, today, Feng Zhang, from China, is helping pioneer the field of gene editing at the Broad Institute. It’s where Moderna, led by Stephane Bancel from France, is racing to produce a coronavirus vaccine. 

None of this happened by chance. Some 2,800 biomedical scientists with PhDs have immigrated to the U.S. every year since 2000, according to a study published in Nature. In 2014, of 69,000 biomedical scientists in the U.S. workforce, 48 percent were US born and the other half were born abroad. 

The United States has made it a national policy to invest more than any other country in the world in science, in its universities, since the end of World War II. That’s one key reason why all of those things happened. But the investment is only part of the story. Like in football, in a discipline so heavily dependent on talent, it takes lots of globally-sourced talent. You need to attract the best people from around the world to come work shoulder-to-shoulder with the US-born talent. It raises everyone’s game.

The numbers alone don’t tell the whole story. There are ingredients in the recipe that only become evident when you take a closer look: freedom, opportunity and a welcoming environment for immigrants. Americans, and Bostonians in particular, are willing to value these more highly than people in other places. If you love freedom and opportunity, and most entrepreneurs do, you are inevitably attracted to the U.S. Entrepreneurs keep coming here, generation after generation, because we feel extremely welcome. This country supports people that take risks and dream big, people who are willing to work hard for a vision of a better future.

U.S. universities and biotechnology companies are the youth academies for future entrepreneurs. They rely on the visa system and welcoming attitudes towards immigrants to recruit foreign talent. They will continue to lead the world in producing biotech entrepreneurs only for as long as the US values immigration more than other countries.

Some elected officials don’t see it this way anymore. US Sen. Tom Cotton, a Republican of Arkansas, said on Fox News over the weekend:

It’s a scandal to me that we have trained so many of the Chinese Communist Party’s brightest minds to go back to China, to compete for our jobs, to take our business, and ultimately to steal our property and design weapons and other devices that can be used against the American people.

So, I think we need to take a very hard look at visas we grant to Chinese nationals to study, especially at the postgraduate level in advanced scientific and technological fields.

If Chinese students want to come here to study Shakespeare or the Federalist Papers, that’s what they need to learn from America. They don’t need to learn quantum computing and artificial intelligence from America.

What Sen. Cotton doesn’t seem to fully appreciate is that many of these visas from China go to people who go on to become American citizens, and to make great contributions to biotech here. Our industry is also global in nature, and relies heavily on strong partners in China and elsewhere. Companies around the world seek to partner with us in the US, because we have done an incredible job of investing in the future, and recruiting the best to come here and pursue their visions.

As President Reagan said in his farewell speech, “We draw our strength from every country and every corner of the world. If we ever closed the door to new Americans, our leadership in the world would soon be lost.”

27
Apr
2020

Capturing Family History, While We Have Time

Leora Schiff, principal, Altius Strategy Consulting

COVID-19 is threatening our families’ present and future. That much is clear.

What may be less clear is that it’s also taking a toll on our past.

Because of the pandemic’s disproportionate impact on our elderly, we are at risk of losing important connections to our family histories.

How many of us have thought they should ask their parents about the stories of their lives “when I have time”. Well, the time is now, before those stories are left untold.

A number of weeks ago (I’m losing track of how many) when we first were asked to stay at home in Massachusetts, my husband and I started spending time digging around in Ancestry.com. I had visited my mother back in January (pre-COVID-19) and had brought back old photos and old family records which I started to organize. My mom is in her 80s (fortunately healthy and safe, despite Governor Kemp’s questionable decision to start reopening businesses in Georgia). I was already trying to capture family history through recorded conversations (putting those primary research skills to good use!). Some of the stories about my mom as a little girl are real gems – who knew she could get into so much trouble as a toddler?

We knew that some members of our family were interested in our family history and had done separate research into old records trying to piece together our family tree and family story. So, we reached out to them.

Little did we know that these early conversations would end up sparking a journey of discovery together.

We now have weekly Zoom meetings to talk about our family history. Actually, I have two weekly Zoom meetings – one for my mother’s side of the family, the other for my father’s. Family members have joined the meetings from across the US, as well as Israel, and Costa Rica; we may have other family from Spain, Australia and Singapore joining future meetings. Some of us have never met; it has been amazing for me to connect with “lost” family (or was I the one who was lost?).

We are exploring what we know about our family, what we think we know and what we don’t know. We are pooling our resources: photos, documents such as passenger records (I am the proud descendant of immigrants from Belarus, the Ukraine and Israel), census records and marriage licenses, and most wonderfully, family stories, memoirs and biographical accounts.

Yesterday, my husband and I had a Zoom call with a couple of cousins to discuss data that we were extracting from a collection of memoirs. I have been building a database of all the people mentioned in the memoirs, along with key characteristics. (This is the consultant in me – when confronted with a mass of information, start making spreadsheets!) We were trying to figure out how to determine potential connections between these people – whether they were related, belonged to the same political, social or religious organizations or had personal social connections – and whether social network graphing could help us with this task.

As we worked through how to set up the database, how we might weight the connections between people (the nodes in our network graph), we were struck by the realization that the four of us were an amazing research team. One of my cousins is a database specialist, with expertise in setting up and curating databases. Her husband is a PhD physicist who has used graphs to study genetic regulatory networks. I’m a consultant, experienced in gathering and analyzing complex data sets and generating research hypotheses. Finally, my husband is a museum exhibit designer, with expertise in building narratives from records and artifacts, interpreting data and objects to help people understand their greater meaning and importance.

It dawned on me that we’re not alone. Many of us are blessed with talented family members. Maybe they live in another time zone, or we only see them once a year or even less. For those of us in the biotech sphere, the analytical capabilities that we’ve honed for our work are easily transferable to this kind of research. Our skills, which may seem so narrowly focused at work, can mesh quite well with people from other disciplines – at least when organized around a common topic of interest such as this.

Some of us have found that COVID-19 has provided some extra free time (no traveling to work, no external social events, etc.). Unlike many people I work with day-to-day, I don’t have to deal with homeschooling kids, so I’ve got the time. For those of you who do have the time, I highly recommend it – in addition to capturing our family stories before they disappear, we have had the opportunity to spend time together as a family. Ironically, COVID has brought us closer together than ever.

And it sure beats doing jigsaw puzzles.

27
Apr
2020

How a Simple Gesture Morphed Into a Full-Time Effort to Feed the Frontline

Ellen Kuwana, founder, WeGotThisSeattle, a volunteer effort to feed the frontline

As a night owl, I relish the “me time” hours from midnight to 2 a.m. Snuggled in bed, the rest of my family asleep, I scroll through the news and laugh at friends’ video posts.

Like many other science writers, I spent many of those quiet hours in February following the relentless spread of the new SARS-CoV-2 virus, especially as my hometown of Seattle emerged as the first US epicenter.

On Mar. 5, I started working from home. The next week, I arranged for my college-age daughter to come home from UCLA. I was relieved when Seattle Public Schools closed and my younger daughter didn’t have to walk down any crowded halls. I wanted everyone home and safe.

My husband, however, is a physician–scientist who does essential work at the University of Washington and a nearby hospital. So we could not all keep entirely safe.

Just one meal for UW Virology

As the UW Virology department scaled up its breakneck efforts to process as many COVID-19 tests as possible, I started hearing from my friends at the university that some of their grad students and postdocs were pitching in at the testing center.

I remembered how tedious it is to pipette all day—right out of college I had worked as a lab tech at the Human Genome Mapping Center at UC San Francisco. As I scrolled through Twitter one night, a tweet from UW Virology landed atop one from a pizza place offering free pizza for healthcare workers.

Something clicked. “Who’s feeding the scientists?” I said to my dog.

She looked back at me as if to say: “Good question.”

On Mar. 13, past midnight again on Twitter, I typed a hurried “Who wants to help me feed UW Virology?” with a #COVID-19 hashtag.

Pagliacci, one of the biggest pizza franchises in the region, responded within minutes. They donated enough pizzas and salads to feed 70 people who were helping out, working long hours and taking extra shifts.

As I drove to deliver the food, I marveled at the lack of traffic, but it also felt sort of weird in Seattle. I greeted the person who came out to load the food onto the cart. She was all smiles. I remember her commenting on how the food would boost morale.

I offered to get the door for her.

“Best not to touch it, or we’ll have to wipe it down,” she said somewhat apologetically.

At first, I thought I would pay for all the food as a one-time gesture of appreciation to UW Virology. But as the adrenaline of that first donation wore off, I started to think more broadly about how to support local medical researchers and hospital workers. It was a bit overwhelming to think of all the medical and research staff in Seattle who were working so hard, day and night, from processing specimens and COVID-19 tests, to caring for patients.

Getting them food was one thing that I could do, and would help to keep their energy and spirits up for a prolonged siege. An army, some famous general once said, marches on its stomach.

Pretty soon, I found myself thinking about this a lot more than just during the wee hours of the morning. With money I was prepared to spend on my own for donated meals, on Mar. 20, I called a friend, placed an order for Rubinstein Bagels and went to buy cream cheese, plates and knives.

People were not social distancing at the grocery store, which made me nervous. I needed to keep myself safe and healthy in order to be able to deliver the food to hospitals safely. Now, to figure out where the bagels could go…

I started working my contacts at UW Medicine, which had closed its hospital to visitors. Through a surgeon friend, after many emails, I reached a point person who could accept the bagels. We did the social-distance dance to unload them onto a cart.

I made a mental note: next time, let the institutional contact unload the food right from my car.

Third meal for UW Virology and WeGotThisSeattle was born

Next time came quickly. I had put up a personal fundraiser on Facebook, inviting friends in Seattle to donate money for meals to UW Virology and other sites. By this time, news was everywhere about the lack of testing nationwide, and our UW Virology lab’s heroic efforts to meet our region’s need for more tests. Within a few days, I had enough donations for a third meal delivery.

Because so many restaurants had shut down, what had started out as a token of appreciation was now more like a lifeline to those who had nowhere else to get a quick bite during their work shift. My original question, “How can I be useful?” was clearly answered. People in the labs posted pictures and thank-you notes on social media. My inbox received a few heartwarming notes. It all confirmed that this was something I should run with.

Pizza, bagels…what next? I remembered Taste of India, one of my favorite local restaurants. On the phone, the explanation of what I was doing had hardly left my lips when the owner interrupted me.

“Ellen, what do you need? We will donate it all.”

His calm, swift response made me choke up.

It was a powerful moment, and not just personally. A tweet I posted describing that act of kindness was viewed by more than 2.5 million people, with more than 31,000 likes.

I can’t explain why this tweet went viral, but I think it has to do with so many of us wanting to help, but not knowing how.

Helping local restaurants

Things took off from there. Donations poured in — donations of funds, but also of food from many restaurants. When restaurants I contacted asked me to pay full price, I happily did. Those that had to ask almost certainly need the funds. And that, too, is part of supporting our community.

From what I’ve heard, many restaurants in Seattle are down at least 80% in revenue. As I’ve picked up food, I’ve seen many places where only the chef and owner (sometimes one and same) are working. They tell me how they hope to hire back their staff, how they don’t know how to make their rent payments. I’ve learned that some of the restaurants that donated food were not in a position to do that, when they were falling behind in their rent.

It all felt quite heavy. But their hope and their eagerness to help feed healthcare professionals and others risking infection to do vital work was also uplifting.

Now when I contact restaurants, I emphasize that I want to help them as well, and it’s OK to charge something for the food. The donated funds enable us to support local business while we feed the frontline.

A recipe for success

With encouragement from friends old and new (and I am forging strong connections with restaurant owners and the point people at the hospitals and UW Virology who have promised me hugs when this crisis subsides) and support from former strangers who have contacted me to help (and I finally got smart and said Yes to offers of help), we are moving ahead with getting systems in place to scale up.

We’re now collecting tax-deductible donations at WeGotThisSeattle. Since starting this project in early March, we’ve raised about $36,000 in donations from individuals. We’ve coordinated food to 30 sites in and around Seattle from 35 local restaurants and businesses, feeding more than 6,300 people. The meals have fueled workers at nursing homes, fire and police stations, and homeless shelters. They have fed bus drivers, EMTs, hospital janitors, and switchboard operators.

I quit my job to focus full time on this volunteer effort. It seemed like time for a change anyway, and I’ll find a new job when this is over. This is the best way I can contribute, right now.

Our meal-delivery effort is one of many: since mid-March, the University of Washington has received more than $300,000 in donated meals from a wide range of groups. The Swedish Hospital system in Seattle estimates that its workers have received 190,000 meals from 280 donors.

I attribute the growth and success of WeGotThisSeattle to four crucial factors:

  1. Contacts to gain access and find the right point of contact at the recipient institution;
  2. Processes that demonstrate your reliability and generate confidence in those partners;
  3. Protocols that food-delivery drivers and recipients follow to keep all involved as safe as possible by preventing any contact with the food during transport and hand-off; and
  4. Social media presence to reach a wide audience.

Thanks to everyone who has contributed to our effort thus far, and to those who are finding their own ways to help.

To Learn More:

  • WeGotThisSeattle.co for media coverage, list of restaurants, sites, and a tax-deductible donation portal (all fees waived until June 30)
  • NASEM Forum on Postsecondary Response to COVID-19

Photo Gallery:

 

25
Apr
2020

A San Francisco Doctor Answers the Call to New York

Ethan Weiss, MD, Associate Professor of Medicine at UCSF; Principal Investigator in the Cardiovascular Research Institute

The week things got really interesting was the week of March 16.

That’s when Sara Cody, the Santa Clara County public health officer, and her legion of public health heroes made the gutsy call – the first of its kind in the nation — to shut things down in the entire 6-county San Francisco Bay Area, home to more than 6 million people. Only two deaths from COVID-19 had been reported at the time. She stuck her neck out there, saying we had to get in front of this pandemic, or else.

That same week, I had agreed to cover the inpatient service for a colleague at UCSF who was advised to avoid the hospital by their physician.

I’m a cardiologist, not an ER doctor. I remember feeling intense uncertainty and fear – mostly fear of the unknown. Everything was eerie and everyone was anxious. We all expected the hospital to be overrun by the weekend. That was how it had happened elsewhere.

When I actually got into the hospital, my fears faded. I got busy and distracted, which created a weird sort of calm. We were just waiting for the surge. I was comforted by how prepared everyone and everything was. Sure, there was concern over lack of PPE, but mostly people were feeling good and seemed focused. There were tons of empty beds. It seemed like we were ready even despite the strange act of waiting for disaster. I don’t remember ever feeling that way before.

And then nothing happened. By the end of the first weekend, the residents were asking for teaching – from me. They were bored. I’ll admit that I started to wonder how long we’d have to wait to know if the surge might not be coming. I was counting days from the lockdown on Mar. 16. I didn’t talk about it at first but I definitely started thinking. No one wants to be overconfident, in that “famous last words” sense.

By the next weekend, I was comfortable to talk about how we were doing well at UCSF. I got this text from a friend on Mar. 26:

“how bad is SF rn? seems quieter compared to nyc”

“It is quieter,” I responded. “I believe that is meaningful. They are still expecting a big surge and are opening closed hospitals, but with each passing day, I get more optimistic. We are now 11 days into the quasi-lockdown, and there has been very little sign of badness at least at our hospital”.

We all played this game for a few more weeks while we were told the surge was coming but it was clear it was not. At the same time, it was clear that other parts of the country were being devastated.

On Mar. 20, I sent this tweet: “I don’t mean this in any other way except genuine concern but I am very worried about what is happening in NY”.

At that point, there were 2,468 cases in NYC.

As of Apr. 24, there are more than 150,000 confirmed cases and over 11,800 deaths. (Source: NYC Health). 

My colleagues and I watched the heartbreaking news from New York like everyone else.

Toward the beginning of April, I started to ask when we would consider sending people from UCSF to help in New York hospitals or to other hard-hit areas. I was told it was too soon. Then on Apr. 10, I tweeted: “Wow @UCSF is sending a team of clinicians to NY tomorrow for a month!”

I was happy. I was happy for New York. They so desperately needed the help. I had talked to friends and colleagues there. They were depleted and tired in every sense of the word. I was also happy for my colleagues – but honestly, I was also jealous.

I was busy. Not busy helping out in the ER at UCSF Medical Center, fortunately. But I was as busy as I have ever been, balancing seeing patients on Zoom with writing papers and grants while also trying to help guide this nascent startup I had helped found just a year and half ago. And then I got very caught up in the story about thrombosis and COVID-19 and have been working on helping to spin up at least two clinical trials to see if anticoagulant therapy could be helpful.

And of course at home, while my two daughters are mostly self-sufficient, there was plenty of work to be done. My wife’s business has been decimated. We are all crowded into a small house and we are doing things we don’t usually do (like clean). There were some amazing upsides and the most notable was spending so much time with the three people that mean the most to me on this planet. One of the most surprising daily joys was making and eating lunch as a family. It feels very European.

But despite all that, I still felt drawn to New York. I mentioned it at a faculty meeting a few weeks ago and was told there was no need for us. Then I heard UCSF was actually going to send a second team and they were asking for volunteers from Cardiology.

I spent at least 24 hours thinking about it. I tried hard to think about all the many reasons I wanted to go and tried as best I could to think about how much was motivated by a genuine sense of mission or perhaps a desire to be in the middle of the action or maybe even from a little envy of my colleagues or maybe even just curiosity or attention-seeking.

I wrestled with it. I finally asked my wife. I reassured her that I was not worried from a health perspective and that I’d be careful. I also acknowledged that it would be a tremendous burden on her to have to parent alone for two weeks in this absurd time, when she’s naturally stressed about her business and the kids are at home all the time. But I also said that everything else could wait. I reminded her that we had planned to take a two-week vacation to Japan in June and that I had numerous meetings and they had all been cancelled and that it was actually a very good time to go in many ways. My lab is basically closed. Most other activities are slow or non-existent. The startup is making it. And the thrombosis trials would/could go on without me.

We also talked about my motives. She grilled me about why I wanted to go, and I told her that I was not entirely sure, but I also told her that I was hearing a dog whistle and it was driving me mad. However, I also said I could not go without her support – her genuine support. After a short time, she looked me in the eye and said, “Ethan, you have to go.”

This “dog whistle” is a mysterious thing to explain. It’s some kind of call of duty, like a ghost of a first-year med school professor whispering in my ear to go. No one is explicitly calling on me, as if I have to go do this. But maybe there’s a little guilt implication in some conversations, as if to say “hmm, wonder why you aren’t getting on a plane to come to New York?”

So I told Jeff Olgin, my division chief, that I wanted to go. He connected me with Michelle Mourad who was managing the process here. By Wednesday, I was credentialed and licensed with maybe 10 minutes of work on my part. Do I have a medical license? Check. It was spectacular.

By Friday, we had a flight scheduled and had an orientation call with the hospital in New York where we are headed.

This morning, Apr. 25, three amazing women joined me in a desolate SFO airport and we boarded a plane. There was a very nice little ceremony. Mark Laret, the CEO of UCSF Health, came and gave a short talk. Sam Hawgood, our chancellor was there, as was Josh Adler and also Kim Murphy, the Director, Special Events & Community Relations at UCSF Health and the person who organized all this.

As our team of four medical personnel gathered in the jetway, we all muttered to each other about how uncomfortable we were with the pomp and circumstance. We just wanted to get there. We wanted to get to work. When we finally got on the plane, we found many other health care practitioners of many stripes from around the Bay Area – ALL of whom were volunteering to go work in NYC. Nobody gave them a ceremony.

So this brings me to the tension I have over the attention doing something like this might bring. I don’t want it to be about me. None of us does. But I also think there is value in telling the story. I think there is value in telling people about how I decided to come, how I feel and some of what I see. I don’t know too much about what I am going to do. I found out yesterday that I will be an attending physician in what used to be a cardiac ICU but that has been transformed (like all ICUs in NY) into a COVID ICU.

I’m not scared of getting sick. I am uneasy about how brutal it will be, tending to wave after seemingly endless wave of critically ill patients. But I will try to stay focused on the task.

What really bothers me is that “first day of school” fear. It’s a lot like how I felt 20 years ago when I came back from the lab to do my clinical fellowship. Will I know what to do? How do I manage a ventilator or volume status? Can I still put in a central line, and will I need to? My wife reminded me this morning on the way to the airport that it’s like riding a bike. But I also have not worked at a new hospital since 2001, so I am feeling uneasy and unsure of myself. There could be slightly different equipment, procedures, colleagues who have already been through the ringer and are moving at warp speed, while I’m trying to get up to speed.

However, all of that is balanced by a strong desire to get in there and get to work. I am excited to learn, to see, to make myself useful.

I’m slightly surprised by the emotions. I did not expect tears at the airport this morning. Ultimately, I am going to miss my family desperately. There is nothing I will ever be able to do to repay them for letting me go and answer this dog whistle.

Over the next two weeks, I will try to write occasionally about my experiences. If I do this right, it will foster a little more understanding of what it’s like on the frontlines. Those of you who know me know that I will be honest and raw and maybe even sometimes crass. But I have such tremendous respect for how people have pulled together to contribute whatever way they can in this wicked moment. This challenge is vastly bigger than any individual effort. I have been trying to remember to thank everyone who has a role to play — from the TSA agents to the custodial staff to the flight attendants (even if they are not serving coffee on this flight!).

It is precisely at times like this that I remember the lesson my Dad taught me when I started my first clinical rotation in medical school now 27 years ago: always appreciate and thank everyone – everyone and most importantly the people who never get thanked.

Now more than ever, there should be no thankless jobs. Everyone has their purpose, everyone is answering a different kind of dog whistle.

24
Apr
2020

A Sad Week of Reckless Leadership

Luke Timmerman, founder & editor, Timmerman Report

The first US death from COVID-19 was reported on Feb. 29.

Today, Apr. 24, the US death toll exceeds 50,000.

That’s more than Italy and Spain combined. Even though we had early warning. It’s tragic.

There’s also a reason why the death toll hasn’t been higher. It’s because of large-scale physical distancing in this expansive country of 330 million people.

After a few weeks, people are understandably getting restless. Tens of millions are unemployed and fearful for their livelihoods. The federal government has thrown up its hands in many respects, passing the buck of leadership to state and local governments. Now we’re seeing a mishmash of local decisions.

The state of Georgia – a place with 10.6 million people, more than 20,000 confirmed infections, and the busiest airport in the country – is led by a Governor that is opening up large swaths of the economy today, relaxing the physical distancing restrictions there. He’s doing that even though his state hasn’t complied with the federal guidelines that say reopening can begin in phases after new infections go through a 14-day decline.

Local decisions like these will determine just how ferocious the second wave of infections will be across the entire country this summer and fall.

Jeff Duchin, MD. Health officer. Public Health – Seattle & King County

“It’s like peeing in one end of the pool. It doesn’t just stay there,” said Jeff Duchin, the leader of Seattle and King County’s public health agency, on a webinar I moderated yesterday for Life Science Washington, the local trade association.

Duchin called the decision of Georgia Gov. Brian Kemp “reckless.” Given the latest models he’s been reviewing, Duchin said he believes the second wave of infection this fall could be two to three times larger in magnitude than what we’re seeing now in Seattle and King County.

Meanwhile, the CDC – once the gold-standard agency in public health — is still AWOL when it comes to coordinating a national testing program. We are nowhere near the number of tests (20 million a day at peak according to one Harvard estimate) we need to be doing to gain the knowledge necessary to suppress the virus with targeted quarantines. Without knowledge from tests, it’s hard to imagine a safe and responsible reopening of the economy.

Still, without any clear idea of where the virus is, we have protestors agitating in state capitols to lift the physical distancing orders. Some people who are sick are even being urged to show up, to exercise their rights as Americans to travel freely. They revel in thumbing their noses at the experts. They’re good at provoking all of us to gape in amazement and horror, good at distracting us from what’s important.

Yesterday, the President suggested that people might want to try ingesting bleach to fend off the coronavirus. Or maybe ultraviolet light.

Talented journalists who could otherwise be investigating breakdowns in our national testing system and kicking the bureaucracy in the rear end are now writing about why it’s a bad idea to drink bleach.

How did we get ourselves into this tragedy? This farce?

How do we get out?

I don’t know all the answers. But I do know that people with education, drive, and good faith – that’s you – need to do constructive things to be part of the solution. That extends beyond this pandemic, and goes into repairing the social fabric, investing in science and education, and helping vulnerable populations. It’s a heavy topic, rethinking citizenship, rethinking what our responsibilities are to our fellow human beings. This will take time to sort out. I believe we can come out the other side better.

Be safe. Be strong.

To borrow a quote from my late father-in-law:

“Be Good to Each Other.”

Science

Testing

  • Contamination at CDC Lab Delayed National Rollout. Washington Post. Apr. 18. (David Willman)
  • Testing Needs to Triple Before Reopening. NYT. Apr. 17. (Keith Collins)
  • Unapproved Tests From China Being Used in 2 States. NBC News. Apr. 16. (Gretchen Morgenson)
  • Antibody Test, Seen as Key to Reopening the Country, Does Not Deliver. NYT. Apr. 19. (Steve Eder et al)
  • Will Antibody Tests Really Change Everything? Nature. Apr. 18. (Smrity Mallapati)

Treatments & Vaccines

  • Novartis is Running a Randomized Study of Hydroxychloroquine. STAT. Apr. 20. (Matthew Herper)
  • A Guide to Disrupted Clinical Trials. BioPharma Dive. Apr. 22. (Ben Fidler)
  • Data on Gilead’s Remdesivir, Released by Accident, Shows No Benefit. Company Still Sees Reason for Hope. STAT. Apr. 23. (Ed Silverman et al)
  • Gilead Statement on Remdesivir Leaked Abstract. Apr. 23. (Gilead Sciences)

Policy

Models

Worth Watching

Policy

  • CDC Director Warns Second Wave Could be Worse. Washington Post. Apr. 21. (Lena Sun)
  • Advice from Abroad for US Governors. ProPublica. Apr. 18. (Stephen Engelberg et al)
  • The Inside Story of how the SF Bay Area Got Ahead of the Curve. Kaiser Health News. Apr. 21. (Angela Hart & Anna Maria Barry-Jester)
  • What Makes SARS-CoV-2 the Perfect Pathogen. The Bulwark. Apr. 21. (David Shaywitz)
  • US Should Allow Volunteers to Get Infected with Coronavirus to Test Vaccines, Lawmakers Argue. Apr. 21. Science. (Jon Cohen)
  • Barr Threatens DOJ Legal Action Against States Over Lockdowns. Bloomberg News. Apr. 21. (Chris Strom)
  • FDA Cautions Against Use of Hydroxychloroquine or Chloroquine Outside Clinical Trials. Apr. 24. (FDA Statement, Repeated on Twitter by Dr. Janet Woodcock).

Humanity at Its Best and Worst

  • Seattle ER Doctor Saved from Cytokine Storm by IL-6 Inhibitor Actemra. LATimes. Apr. 13. (Richard Read)
  • In Pursuit of PPE. New England Journal of Medicine. Apr. 17. (Andrew Artenstein)
  • Healthcare Workers Stand Against Lockdown Protestors in Colorado. NBC News. Apr. 20. (Ben Kesslen)
  • Pandemic Victims. Sick & Dying, but Not from The Virus. NYT. Apr. 20. (Denise Grady)
  • It’s My Job to Call People To Tell Them They Are COVID-19 Positive. STAT. Apr. 24. (Caroline Schulman)

TR Coverage

  • Build Back Better. Apr. 22. (David Shaywitz)
  • Massachusetts Biotechs Consider How to Return Safely. Apr. 22. (Adam Thomas)
  • Singapore’s Crisis: How It Forgot to Check Its Blind Spot. Apr. 21. (Carolyn Ng)
  • How to Navigate a Blizzard of Antibody Studies. Apr. 21. (Ruth Etzioni)
  • Cultivating a Tolerance for Adversity. Apr. 20. (Eric Murphy)

Personnel File

Rick Bright, the head of the US government’s Biomedical Advanced Research and Development Authority (BARDA), a key unit for vaccine development, abruptly left his post. He later filed a whistleblower complaint, saying he was being sidelined by the administration because of his unwillingness to promote unproven therapies. See his statement.

Greg Guyer was hired as chief technical officer and EVP of global manufacturing and technical operations at BioMarin Pharmaceutical. He was formerly SVP of operations at Bristol-Myers Squibb. He takes over from company veteran Robert Baffi.

Investing

  • Value Creation and Destruction. Biotech IPO Performance. LifeSciVC. Apr. 17. (Bruce Booth)
  • It’s Time to Build. A16Z Blog. Apr. 18. (Marc Andreesen)
  • Big Pharma Calls for Billions in Upfront Coronavirus Funding. Apr. 20. Financial Times. (Andrew Jack)

Financings

Cambridge, Mass.-based Affinivax, a vaccine developer with a lead program for pneumococcal infections, raised $120 million in a Series B, led by Viking Global.

South San Francisco-based ORIC Therapeutics, a company working on cancer resistance, raised $120 million in an IPO of 7.5 million shares at $16 apiece.

Lexington, Mass.-based Accent Therapeutics, a cancer drug developer focused on RNA-modifying proteins, raised $63 million in a Series B financing. EcoR1 led.

San Diego-based Arcturus Therapeutics, an RNA-based medicine developer, raised $80 million in a stock offering of 4.7 million shares at $17 apiece.

San Francisco-based Nitrome Biosciences raised $38 million in a Series A financing co-led by Sofinnova Partners (the European-based venture group) and AbbVie Ventures. The company is working on Parkinson’s disease.

Bethesda, Maryland-based Aledade raised $64 million in a Series C financing to continue expanding its network of physician-led Accountable Care Organizations. OMERS Growth Equity led.

San Francisco-based Unlearn.AI, a company that creates ‘digital twins’ to serve in clinical trial control arms, raised $12 million in a Series A. 8VC led.

Deals

Ann Arbor, Mich.-based Esperion Therapeutics pocketed $60 million upfront from Otsuka Pharmaceuticals as part of a deal to commercialize its two new cholesterol-lowering products in Japan.

Gilead Sciences struck a three-year collaboration with oNKo-innate to work on engineered Natural Killer cell therapies for cancer.

Veracyte announced an exclusive license from Yale University to develop the first genomic test for idiopathic pulmonary fibrosis, based on a 52-gene signature.

Regulatory Action

The FDA gave the green light to Incyte to start marketing pemigatinib (Pemazyre) for patients with locally advanced or metastatic cholangiocarcinoma. The drug is made to target fibroblast growth factor receptor 2 (FGFR2) fusions, which are detected by the FoundationOne CDx test.

Sanofi got FDA clearance for a new quadrivalent meningococcal vaccine.

Data That Mattered

Exelixis and Bristol-Myers Squibb reported that they hit the primary endpoint in a clinical trial of patients getting their first round of treatment for renal cell carcinoma. Patients got the combo of nivolumab (Opdivo) and cabozantinib (Cabometyx), and were evaluated for progression-free survival, overall survival, and overall response rate. Details to come at a medical meeting.

AstraZeneca and Merck’s PARP inhibitor, olaparib (Lynparza), passed a Phase III trial for men with advanced metastatic, chemical castration-resistant prostate cancer. The study looked at men with homologous recombination repair gene mutation (HRRm). Data to come at a medical meeting.

Tweetworthy

Someone we all need a little gallows humor.

Sometime you laugh, sometimes you cry. Sometimes you just have to slap your forehead.

“Some experts say” it’s bad to drink bleach. Golly, you don’t say?

And sometimes members of the evidence-based, reality-based community decide they have to get involved in the debate, however messy and ugly it can sometimes be.