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Peter Kolchinsky, managing partner, RA Capital
Will the world care how we beat COVID-19 – whether with a drug we make from scratch or an older one that turns out to get the job done? As people concerned for our families, we all know the answer. Just get it done!
But as drug developers, let’s be honest that it doesn’t feel quite as heroic unless it’s really novel.
I think we may have developed an unhealthy, facile relationship with the word “novel,” looking to it for security against the attacks on our industry that, while deserved by some companies, seem indiscriminate at this point. As if experiencing Stockholm Syndrome, we are on the brink of accepting the public’s notion of novelty at the expense of the novelty that really matters.
After years of being ridiculed by Congress, the media, and the public as highly profitable, greedy, and not innovative — merely retweaking old drugs — it’s no surprise that the drug industry would want to emphasize all of the incontrovertibly novel breakthroughs of late. Gene therapy is hardly a modest tweak. Neither are RNAi, antibody-drug conjugates, and protein folding correctors. Those who are working with technologies like these can rightfully claim the term “novel” in the most straightforward way most people mean it, which is to say “never before seen” or “had to be developed from scratch.”
Many of our industry leaders believe that pursuing such novelty should be the industry’s sole purpose. Recall the letter signed by over 200 biotech CEOs in January that promised:
“We will invest only in novel therapies that address unmet patient needs.”
If indeed we did that, presumably the public would have a harder time claiming that high drug prices are unjustified because the drugs weren’t innovative-looking enough, so I can understand the merits of this imperative.
The reality is that the public doesn’t actually care about novelty. The public only claims to care, or maybe only thinks that it cares. Consider the urgency with which the public has looked to innovators to come up with treatments for COVID-19. Companies are running new discovery programs and screening for novel inhibitors of various viral components. I have no doubt some of these programs could eventually succeed, but they are far from the market and each faces long odds.
Meanwhile there are already dozens of older drugs, including many generics, being tested individually or in combination for the treatment of COVID-19. Dozens more older but unapproved compounds, like Gilead’s remdesivir, that failed in their original indications, are being reheated. If we’re lucky enough that any of those programs really can reduce the severity of the disease, keep patients out of hospital, and/or save lives, then the world will have been saved by… drug repurposing.
Yes, we could end up saving lives with an old drug that most people wouldn’t consider “novel.”
Does that mean developing those drugs for COVID-19 will have been easy? No. Without risk? No. Inexpensive? No.
Will it matter to the people whose lives are saved and to everyone who will be able to come back to work once the pandemic is resolved that their salvation wasn’t “novel”? It absolutely shouldn’t, though some of the harshest critics will never be satisfied, but the vast majority of people would be grateful. And certainly all of us in the drug industry should know better than to denigrate a COVID-19 treatment simply because it didn’t require inventing a new drug from scratch. We should be so lucky.
COVID-19 might just leave us with a novel definition of the word “novel” that we’ve long needed. Specifically, all anyone should care about is whether we’ve addressed an unmet need. That’s what society should reward, and that’s what our industry should commit to doing.
Whatever therapy or intervention solves a previously unmet need is inherently novel. Any treatments for COVID-19, that turn out to work will be “novel” in every way that matters.
For many in our industry, swearing by novelty is a means of, let’s say, #socialdistancing themselves from notorious drug companies that the public reviled for charging high prices without engaging in almost any actual drug development. Here I’m thinking of the Marathons and Belchers of the world, which, seeing no competition from altruists, stepped up to earn high rewards for doing low-risk paperwork the FDA needed someone to do.
Though they make for bad press, we mustn’t overreact to these fringe cases. If we feel that the few outliers like this are a stain on our names, we should push for reforms that empower the FDA to contract with a nonprofit to, for example, get a foreign generic drug licensed, labeled, and marketed in the US at a low price so patients don’t have to illegally import it. Turning our noses up at Marathon and Belcher just because their work didn’t seem novel enough to merit a high price is not only unproductive, the unintended consequences could be counter-productive.
Here’s the harm of committing to “novelty” at all costs. Imagine if a company suspected it could repurpose a low dose of an old generic HIV drug combined with an old generic epilepsy drug to treat a different neurological disorder. They know the combination would likely be safe because the drugs, as single agents, have already been in millions of patients. Yet studies would still need to demonstrate efficacy in the new indication and determine proper dosing limits. But the company would worry that payers, enjoying the support of a jeering public conditioned to denigrate anything that isn’t clearly novel, will refuse to pay for this combination drug. The company might fear that insurers would tacitly nudge physicians to prescribe the old generic drug components together, failing to reward the company that invested significant time and money in teaching the world about the medical value of this new drug combination. Would it risk the ridicule and financial uncertainty of repurposing these generics?
Or would it instead develop an entirely new molecule that does the same thing? That would take longer and be riskier. The final product would have a high price, and payers might resent having to pay, but at least no one could say that the product wasn’t “novel” in the conventional sense.
What would patients want? A safe and effective treatment they can afford. In other words, for insurance to pay for whatever works. So what should society want? The same.
To the extent that the public, the media, and Congress are concerned about novelty, it’s because it’s a litmus test for whether they think an innovation deserves to be rewarded with a high drug price. The corollary is if it’s not novel, then calls for price controls are fair.
The public, the media, and Congress are outraged over drug prices because many patients can’t afford the treatments they need. Unfortunately, society has collectively misdiagnosed the reasons drugs are unaffordable. It isn’t systematic price gouging by drug companies (the industry’s profit margins are too modest to tolerate even a 20% cut in US drug prices); it is, has always been, and continues to be America’s terrible insurance coverage. While many Americans do have good insurance and can afford their copays, some are crushed by their out-of-pocket costs, and ~15% of Americans have no insurance at all. Nothing about healthcare is affordable without insurance.
If there were ever an illustration of how stupidly counter-productive America’s health insurance designs are, recall the people who dutifully reported for COVID-19 testing and were sent home with massive bills, deterring others from seeking testing at all. They went home, or back to work, and unwittingly started spreading the new coronavirus. And even when ordered to cover COVID-19 testing, some payers interpreted that narrowly, sticking patients with bills for necessary but ancillary tests, such as those for flu, that doctors would order to help them interpret COVID-19 testing results. We all see the absurdity of that because we know that testing is essential for our collective public health. We’re outraged that payers, as our chosen agents for making appropriately-prescribed care affordable, are deterring healthcare that is essential for the public health.
But what’s true for COVID-19 and for testing is also true for all diseases and all treatments. And while it’s not as obvious as with COVID-19 coverage, affordable healthcare for all diseases for any individual is also a public health issue for all. When payers don’t cover insulin well enough for patients to afford it, then some will ration it and suffer. Later, when they go blind because they couldn’t afford to manage their diabetes, the added cost of that care is unavoidable. Yet so much individual suffering and societal cost could have been avoided had the insulin been covered properly by the insurer in the first place. It’s an example of being penny wise, pound foolish.
So let’s recognize that the pressure that we as drug developers feel to only develop and charge for what society agrees is “novel” is really an outcry over two things.
First, we need proper insurance to make all appropriately-prescribed drugs affordable for everyone. Second, the pharmaceutical industry should only develop and charge America high prices for products that solve problems that are still unmet by all the known uses of our existing armamentarium of generic drugs (which, with few exceptions, it already does – just consider how impossible it would be to even run a trial for a new drug that aspired to be no better than a statin).
Society doesn’t want anyone playing games with REMS programs to price-jack an old, off-patent drug for the same old use, as Turing notoriously did with Daraprim. But the public does want biosimilars. By design, those aren’t novel, but they will bring down drug prices. The public doesn’t want companies exploiting ASP+ loopholes in Medicare Part B reimbursement to enjoy high revenues from branded drugs that are undifferentiated from generics. But it does want fast-followers (aka me-too drugs) in new classes that offer a greater variety of treatment options and drive price competition, as has happened with PCSK9s, SGLT2s, GLP-1s, CGRPs, and and many of the other acronyms we’ve ever drugged. Consider that America would have enjoyed greater negotiating power and discounts from Humira had there been a comparable me-too; developing competitors to branded drugs should be encouraged, not shunned by a commitment to “only invest in novel therapies.”
So what should we as an industry commit to so that it shows that we are aligned with what society really wants and deserves from us?
I propose this:
We will invest in drug development to address healthcare needs that are not yet met by the known uses of generic drugs.
Some might not find this satisfying because it doesn’t include the word “novel,” which the public likes to hear. Yet this statement captures everything we are doing to solve COVID-19 as quickly as possible, including new drug discovery and old drug repurposing.
And this statement applies to all of drug development for all our remaining unmet needs. Whether that means we will repurpose an old drug for a new use, reformulate an old drug to make it safer or more effective, invent an entirely new drug, or launch a similar competitor to another branded drug, it’s all in the public’s interest.
As long as all Americans are properly insured with affordable (or no) out of pocket costs, they will all be able to get the care they need. And as long as all those drugs go generic without undue delay — which means patents expire when they should, and aren’t extended through patent gamesmanship — then America and the world will be getting value for its money. I’ve written elsewhere, including a book, proposing specific reforms to shore up genericization for all drugs that would spur innovation.
So let’s either retire the word “novel” or at least resist the urge to cave to the public’s old notions of what it means. The COVID-19 crisis has primed the public to appreciate both the value of having an armamentarium of approved drugs and the benefits of searching for new uses for them. Let’s therefore learn together to see all solutions of important unsolved problems as “novel, in every way that matters.”
Peter Kolchinsky, a biotechnology investor and virologist, is Managing Partner of RA Capital Management, L.P., and author of The Great American Drug Deal.
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Kristin Anderson, postdoctoral fellow, Fred Hutch
“When I was a boy and I would see scary things in the news, my mother would say to me, ‘Look for the helpers. You will always find people who are helping.’” – Fred Rogers
The Seattle scientific community has always been tight-knit and collaborative, but we have mobilized like never before to respond to the threat of COVID-19. My friend and fellow Climb to Fight teammate, Bob More (@Bobmorevc), recently wrote an excellent piece recognizing a number of Unsung Heroes in this battle.
My hope is to share just a few stories of people working behind the scenes which you may not have heard yet. From the scientists who led the charge to make testing widely available, to the community members who have stepped up to support all of their efforts – we see you. And we are grateful.
Here are just a few stories to highlight how our Seattle community has come together to support each other.
Dr. Helen Chu (@HelenChuMD) is an infectious disease expert and the lead scientist for the Seattle Flu Study (@seattleflustudy). In short, the project asks volunteers in the community with flu-like symptoms to send in nasal swabs. Her team of scientists studies those samples to learn more about the flu.
Dr. Helen Chu, assistant professor, allergy and infectious diseases, University of Washington
In January, when the outbreak in Wuhan, China was in the news, Dr. Chu hypothesized that the coronavirus was already in the United States and being transmitted through the community, not just by people who had recently traveled to the US from China. She asked Washington state, the Centers for Disease Control and Prevention, and the Food and Drug Administration for permission to test the Flu Study samples for the novel coronavirus. The samples and all the infrastructure to study them were already in place. The study was up and running, collecting samples. It wouldn’t take much to shift gears to look at those same samples for the new virus. But Dr. Chu was firmly denied. That wasn’t part of what participants had signed up for. A new consent form, potentially taking weeks or months, would normally be required to move ahead on such a major amendment to study protocol.
Dr. Chu considered the ethics of the situation. This was a fast-moving and deadly pathogen. She discussed it with colleagues. Ultimately, she decided to test for the novel coronavirus anyway. They couldn’t wait any longer. Her results, from samples tested Feb. 25, are the reason we know the virus was spreading undetected through the community in Washington state. Her results are the reason that public health experts began sounding the alarm about the virus in the United States. Her results are also the reason we now have the Seattle Coronavirus Assessment Network (SCAN) program, the first coronavirus surveillance program in the country, which can begin to assess the basics of how many asymptomatic spreaders we have in the community, and where they are, so they can be isolated. Like the Seattle Flu Study, SCAN utilizes simple nasal swabs that community members can perform at home. Dr. Chu’s decision to persevere has been instrumental in our fight against this virus.
Keith Jerome, head of UW Virology division
Equally important in the early stages was the work of Dr. Keith Jerome and Dr. Alex Greninger, experts in virology at the University of Washington (@UWVirology) and Fred Hutchinson Cancer Research Center (@FredHutch). Shortly after the new coronavirus was being discussed in the news, they realized the country needed a diagnostic test for the virus and decided to divert some of their lab resources to develop one. When the Centers for Disease Control and Prevention’s tests did not work, these UW / Fred Hutch scientists applied to have their lab, and the test they developed there, certified by the Food and Drug Administration. That way, they could perform diagnostic tests for healthcare providers across the country. Their decision to develop a test using their own resources, even if it had not ever been needed, is saving lives every day.
This is not the norm for a research lab to turn itself, virtually overnight, into an industrial-scale high-volume diagnostic testing facility. Normally, they’d focus entirely on research questions, such as incubation times for a new virus, viral shedding rates, or various modes of transmissibility. They put their horsepower into doing an industrial task for patients in need in our community because somebody had to do it.
Once their clinical lab was approved to run patient samples, their small team started running diagnostic tests as fast as humanly possible. But even at peak speed they could only run about 200 samples per day. Knowing they needed to ramp up their throughput, they purchased machines to automate some of the process, but there were some steps that still needed to be done by hand. UW Virology put out a call for help. The Seattle science community answered. Volunteers from a variety of scientific disciplines, many of whom are young graduate students and post-doctoral fellows, set aside their own research to learn molecular virology techniques so they could process patient samples and open up the bottleneck. These volunteers are currently working in shifts around the clock and have helped increased the lab’s throughput to a maximum of more than 3,000 patient samples per day.
Processing thousands of samples is a massive undertaking. Administrators from multiple departments at the University of Washington quickly began volunteering their time providing logistical support. Almost immediately, the lab realized they were short on a critical lab supply: pipette tips. They again sent out a blast for help, this time on social media. Within 24 hours, local research labs and Roche (@Roche) delivered thousands of tips.
In response to the request, members of the community also reached out asking what they could contribute. One generous volunteer made hundreds of bags of healthy snacks for the researchers to “grab and go” between processing samples. Portage Bay Café (@portagebaycafe) donated breakfast, Starbucks (@Starbucks) donated coffee, and Pagliacci Pizza and Taste of India donated dinner for all the volunteers. Ellen Kuwana (@EllenKuwana) organized a Facebook Fundraiser and to date has raised over $15,000 to provide meals for the lab volunteers and healthcare workers while simultaneously supporting local restaurants.
Pavitra Roychoudhury
Once the clinical lab received the first sample containing coronavirus, bioinformatician Dr. Pavitra Roychoudhury (@pavitrarc) led UW Virology’s effort to analyze the complete viral genome in each of the local samples. Their goal is to develop a better understanding of transmission dynamics and viral genetic diversity. To do that, they plan to sequence every positive sample run in the clinical UW Virology lab. So far, they have deposited over 230 sequences to the Global Initiative on Sharing All Influenza Data (@GISAID) database. With sequences from this database, Dr. Trevor Bedford (@trvrb) and the team at Nextstrain (@nextstrain) construct a map of global transmission dynamics and viral evolution. These sequences are now open to the international scientific community to study, and to help other locations get a jump on the virus that’s likely headed their way.
Importantly, sequencing, assembling, annotating, and depositing sequences in these databases is no small feat. To speed up this data sharing, UW Virology again put out a call for support. Within 24 hours, they had dozens of offers from people with computational expertise volunteering their time. This collaborative effort to make data available as quickly as possible is a sea change in how scientific findings and data are often shared. Science and knowledge are being made freely available, and in real-time. There’s no waiting around for six months to get your manuscript published. It is inspiring.
The timing of this massive open science movement seems particularly appropriate. In an age when misinformation is so widely available on the internet, many people have been turning to scientists for answers. Community members are offering appreciation and virtual support through social media to scientists who they might otherwise not meet, or might not understand well in normal times. Parents are sharing that their kids want to be scientists. People are raiding their homes for supplies to donate, like masks, hand sanitizer and disinfectant wipes, which are desperately needed by caregivers in local clinics and hospitals. For people in the lab or the clinic, working long days and putting their own health at risk, gestures like this provide an immeasurable morale boost.
We are all contributing to something monumental that will likely be the defining events of our lifetimes. I could not be prouder of my friends, colleagues, and community. #WeGotThisSeattle #WeGotThisWA
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Carolyn Ng, managing director, Vertex Ventures HC
A week ago, I wrote an article for Timmerman Report on Singapore’s COVID19 response, and how the country has kept its cases low with no COVID19-related deaths.
In that article on Mar. 19, I elaborated on how Singapore had not ordered any businesses to shut down. Instead, the country had kept the number of cases low over the last few months through early and aggressive targeted containment policies, which were reinforced and implemented with high efficiency before cases surged.
That’s all changed in one week.
Literally a day after my article was published, it was announced that two patients (a 75-year-old female, and a 64-year-old male) died in Singapore from COVID19-related complications. Not unexpectedly, the country is now facing a second and larger wave of case spikes. The main reason for the surge in cases is coming from Singaporeans and long-term residents returning home from the UK and US, where uncontained outbreaks have clearly been raging for weeks, largely undetected. At this point in writing, Singapore has reported a total of 732 confirmed cases in the country – more than double from 313 a week ago.
Something Else You Need to Know About Singapore — Not Shown in “Crazy Rich Asians”
A little blurb on Singapore, this small, densely populated city state: we gained independence from our British colonial masters in 1946 after WWII and Singapore joined the Federation of Malaysia in 1963. In 1965, Singapore was expelled from the Federation of Malaysia as a standalone country with absolutely no natural resources, not even a clean water supply of its own. Every Singaporean grows up being intimately familiar with the famous historic scene of our former Prime Minister Lee Kuan Yew shedding tears into a piece of tissue when he announced the separation of Singapore from Malaysia as he had grave concerns for the survival of the island state.
I often hear my tourist friends complain that Singapore is “boring,” that there is nothing else to do in the country other than walking down Orchard Road, the shopping mecca of the country lined with gigantic shopping malls, one after another.
To them I calmly say: as you look around these ridiculously clean surroundings, which some criticize as “overly sterile,” please bear in mind that you are in fact standing on the ground of a miracle of an economy. Within a few mere decades, Singapore transformed itself from third world to first world. It is now one of the highest-ranking countries in the world in terms of GDP per capita. All that with zero natural resources.
That also means one thing: the country’s service and trade-dependent economy is all it has to ensure its survival and prosperity. The economy is its bloodline. Officials there think very carefully about how to best balance public health and the country’s economy.
Singapore’s Hybrid Model: Not (Yet) a Full Lockdown, But “Don’t Play Play”
In view of the second wave of case spikes in late March, Singapore took tough new steps to curb coronavirus spread. There are two specific objectives. One is to isolate and reduce imported cases. The second is to slow down community transmission.
1. Stemming Imported Cases: Borders Closed and Stringent Isolation of All Returnees
Singapore is an important transportation hub, with a significant fraction of its GDP generated from its airport and shipping ports. Last week, the government took the painful step of shutting its borders to all short-term visitors. Only long-term work pass holders working in essential sectors such as healthcare and transportation are allowed re-entry into the country.
As for Singaporeans and Singaporean Permanent Residents returning home from abroad, every single returnee is made to serve a 14-day isolation notice – with no exception. In particular, Singapore residents returning from the UK and the US are taken from the airport to designated hotels directly with special transportation arranged by the authorities to minimize their human contact during the commute. Accommodation and all meals are to be provided for by the government.
There is a common Singlish lingo used by us Singaporeans, known as “don’t play play,” which literally means “don’t mess around with me.” Consistent with that spirit, the Singaporean government means it when they serve you a 14-day stay home (or hotel) notice. Spot checks are done via text messages, video calls and surprise visits. People can choose to wait for two weeks before heading out to their favorite chicken rice stall, or face jail time of up to six months and/or up to a $10,000 fine in Singapore dollars. In just a few days, 89 work passes have already been revoked by the government for flouting stay-at-home notices.
2. Curbing Community Transmission: Stepwise Approach in Social Distancing
Singapore’s multi-ministry COVID19 task force has announced mandatory closures of bars, cinemas and all other entertainment outlets from Mar. 26 to Apr. 30. These are the island state’s most draconian measures yet. The order also include suspension of tuition centers, religious services, and gatherings of more than 10 people.
Is the country now considered to be in “lockdown” or even a partial lockdown? No. Schools have thus far remained open. Restaurants have been required to create more space between patrons, but they do remain open. Working-from-home is not mandatory, but has become the norm. Except for those served stay-at-home notices, other residents are not required by law to stay at home.
In a typical Singaporean fashion, even in the absence of a lockdown, the government is unmistakably serious about its social distancing measures. One just need to look at the headline splashed across Singapore’s Straits Times (the country’s most dominant media channel) yesterday:
Lockdown or Not?
Not surprisingly, given the various forms of lockdown/shelter-in-place in various cities around the world, people are questioning if Singapore should be more strict, and start enforcing a full lockdown immediately.
When asked that question at a press conference on Mar. 24, co-chair of Singapore’s COVID task force Lawrence Wong explained that Singapore’s measures have been designed, right from the beginning of the COVID19 crisis, to be meted out in tiers and in response to close monitoring of fast evolving risks.
The intent of the Singaporean government has always been, from the beginning, to introduce targeted containment measures early, swiftly and decisively so that the country will be able to nip the spread in its bud without triggering an emergency lockdown that will bring the country’s economy to a halt.
BUT, before I go any further, let me emphasize that this decision was taken by Singapore in January when the world first heard of COVID19. Most parts of the world ignored it at that time.
To put things in perspective, Singapore currently has, since the first reported case in January, a total of only 732 confirmed COVID19 cases, and two COVID19 related deaths. The magnitude of the COVID19 crisis in Singapore, even with the second surge (and adjusting for population), does not come close to the crisis that’s unfortunately occurring in the United States. Since the world first heard about COVID19 in January, the US has largely responded with delays and inaction. As of this writing, the US now has the most confirmed cases in the world — more than 87,000 — exceeding both Italy and China. More than 1,300 Americans have died, and the numbers are increasingly rapidly every day.
So, please, my dear American friends, please do not point to my beloved country Singapore as an exemplar of how to best balance public health and economic prosperity.
Yes, Singapore has managed to keep its schools and businesses open, economy running AND cases low. Some people argue that the US can do the same. But that’s impossible. The reason is that, simply, for many parts in the US, such as New York, it is too late: we have lost the window of opportunity for less drastic measures. A virus that spreads with exponential speed, and which has been spreading nationwide without containment for weeks can no longer be contained. It can only be mitigated with the kinds of extraordinary physical distancing and shutdown measures that are currently being employed in a number of states and localities. However, some of the other strategies deployed in Singapore may still be applicable and useful in the US, which the following sections will describe.
Saving Lives with the 3Ts: Test, Track and Treat
While the world awaits a prophylactic vaccine, the “3Ts” approach of test, track and treat remains the gold standard. Singapore is throwing its weight aggressively behind these efforts.
Last But Not Least, Saving Livelihoods
Returning to my earlier introduction of Singapore, with no hinterland and no natural resources, Singapore’s trade-dependent economy is the country’s lifeline. Deputy Prime Minister Heng Swee Keat announced an unprecedented COVID19 Resilience Budget of $48B Singapore Dollars package to carry the country through this difficult time. Another $17B Singapore dollars in stimulus will also be drawn from Singapore’s past reserves, increasing this budget to 11% of the country’s GDP.
I am not an economist, so most of the finer technical details were lost on me as I watched the parliament session in which this budget was worked out. What did catch my attention was:
The Worst is Not Over
I said it last week, and unfortunately I will have to say it again: the worst is not over – not for Singapore, and certainly not for the US or the rest of the world.
May the strong carry the weak, may the wise lead the way for the masses, and may the masses stay on their couches, for now.
Disclaimer:
This article expresses the personal views and perspectives of the author. The views and perspectives expressed here do not necessarily represent the views or perspectives of Vertex Ventures HC, or any officer, director, partner, member, manager or employee of Vertex Ventures HC, or any of its affiliated entities.
David Shaywitz
One consequence of the present crisis is the urgent embrace of telemedicine, as I recently discussed. Whether the adoption is sustained beyond the crisis period remains to be determined, although use seemed to be increasing overall even before the pandemic hit.
As more physicians and patients find themselves pressed to adopt telemedicine, I thought it might be helpful to better understand what this transition and experience is like, first-hand. So I asked my brother Jonathan, a psychiatrist in Los Angeles and a relatively early adopter of telemedicine, about his experience.
Jonathan is an adult psychiatrist, with a focus on anxiety and affective disorders (depression, bipolar, mood disorders), and a particular expertise in psychopharmacology.
Here is what he had to say.
Jonathan Shaywitz, psychiatrist, Los Angeles
Timmerman Report (TR): For starters, help us understand what you typically cover with patients in a (pre-COVID) in-person visit?
Jonathan Shaywitz (JS): Most visits are follow-ups, tend to be extremely targeted, about 15-20 minutes long, and focus on medication management, following up on side-effects, for example. There’s no physical exam; the questions are generally subjective.
TR: How did you first get involved in telemedicine?
JS: About six years ago, I was medical director at a Southern California hospital system with two large hospitals, half an hour from each other. At the time I joined, the hospital had already installed a telemedicine capability to enable staff at one location to see emergency room (ER) patients and floor [in-patient] consults from the other hospital – you could provide care from one site while physically being in the other. Most importantly, this allowed the ER staff to get in touch with a psychiatrist right away, so it wouldn’t delay the care of patients, and interrupt the flow of ER patients waiting to be seen. In many ER settings, a common hold-up can be waiting for a psychiatrist to come and evaluate a patient.
TR: When you first heard about this set up, were you skeptical? Interested?
JS: I was both interested and skeptical. I was especially skeptical about the technology, because you are really relying on it. I am at my desk at one site, and on the other end, they are wheeling a robot with a video screen with you projected on it. You are counting on the fact that the robot is available and functioning – plus you need someone to appropriately set up the machine. In my experience, this tended to work very well in the ER – basically because there was a single person responsible, and they were very familiar with the technology. Floor consults tended to be more challenging – depending on the floor, you might not have someone around who really knew how to set up the technology.
TR: Do you feel you were able to do as good an exam remotely as if you had seen the patient in person?
JS: I do. There were no procedures involved. Emergency room patients tended to be especially accepting because they were so happy to see a psychiatrist and not have to wait – there was a real sense of time being an issue. The typical evaluation would be for acute depression, often focused on the question of whether the patient was at risk for self-injury.
TR: Seems like a high stakes evaluation to do remotely – did you feel comfortable, and was it a difficult adjustment?
JS: I did feel comfortable, and it didn’t seem like a difficult adjustment, at least not in this setting, because the exam is so targeted and focused, and the patient is in a well-controlled environment. Floor consults were a little more challenging, both because of the technology issues I mentioned earlier, and also because the consults could be more vague, and less focused.
TR: Did you feel that on these floor consults, you were able to be as effective when you used the robot?
JS: It can be a little more difficult; when you consult in person, you often are dependent on collateral information, such at what you might learn from a family member who’s nearby or waiting outside. It’s harder to get some of that information when you’re using the robot.
TR: You went on to use telemedicine extensively in out-patient psychiatry; what was that experience like?
JS: In the outpatient setting, you can’t control the environment, in contrast to the hospital ER and floor consults. You’re at the whim of the patients, and often they take it a little less seriously. When patients come to the doctor’s office, they tend to be more focused, and in the moment. The big advantage of telemedicine, of course, is the convenience, but this can also mean a patient is multitasking, or not speaking from a conducive location. Many telemedicine doctors talk about this challenge. I’ve had patients who would be talking with their friends, watching television, or just in a crowded place. This is a problem not only in terms of security and privacy, of course, but also, at least as importantly, because the patients tend to be distracted by the environment. Telemedicine doctors try to manage this by setting limits and having boundaries.
TR: So given all this, what’s your view of telemedicine?
JS: I encourage it. Even with all the challenges, it is still better than people not being able to make it to appointments. The overall quality of care you can deliver because of the continuity more than makes up for the occasional challenges of a session.
The overall quality of care you can deliver because of the continuity more than makes up for the occasional challenges of a session
TR: How do you have to adjust your style for telemedicine?
JS: You need to be more structured with patients. You also have to set limits.
TR: For your outpatient interactions, was technology an issue?
JS: No, not at all – we used a HIPAA-compliant app, which worked extremely well.
TR: What about reimbursement – it sounds like that can be a problem for many?
JS: When I first started, some insurance companies would only reimburse for face to face encounters – but that’s really improved now.
TR: And is there a requirement for an initial meeting face to face?
JS: Initially that was true, but it seems to have gotten relaxed over time for many payors. Often, it’s the physician that wants the initial meeting in person.
TR: Finally, what do you see as the future of telemedicine?
JS: Even before COVID-19, telemedicine was skyrocketing. It is the future, especially in areas like psychiatry. Because it’s not procedural, the major factor is convenience – time and geography – and telemedicine allows patients to fit in appointments much more easily. The key needs are checking in and continuity, and telemedicine affords this.
Luke Timmerman, founder & editor, Timmerman Report
When a story moves with exponential speed and deadly force, it’s hard for a human being to keep up.
Hard for you, and hard for me.
My approach these past few weeks has been to work with purpose and passion on this story that touches all of humanity. The plan has been to seek out diverse voices with fresh perspectives on the pandemic, recruit them to write for TR, and aggressively edit and publish their work in addition to mine. All of the pandemic coverage is being made completely free (no ads, no subscription required), so you can share this quality coverage with family, friends, and colleagues. I am grateful to see so many of you appreciate it.
Human life is on the line. People need quality information to make the best decisions in their daily lives. Journalism always has a public service duty, but it’s never more important than times like now. That’s why everything on Timmerman Report related to the pandemic is being made free, so you can share it with your loved ones, friends, and colleagues who need quality news and information, as opposed to the propaganda and entertainment that tends to drive too much public discourse.
My hope is that in the weeks ahead, you can count on TR to keep things in perspective, while you do what you have to do to keep your families safe and your companies operating under stress. Expect a mix of informative, data-rich voices, and fresh perspectives that can help guide us all through the crisis. Knowing the emotional strain the pandemic puts on people, expect these pages to also shine a light on writers who tap into the human dimension which is too often overlooked in the business world. You may even get a dose of humor once in a while, like yesterday’s piece by Lisa Suennen.
As a Timmerman Report subscriber, I want you know my inbox is open to you. I’m listening.
If you have suggestions of people and ideas that I should consider, let me know. luke@timmermanreport.com.
Now on to your regularly weekly Frontpoints.
The Table That Has Me Most Worried
The US healthcare system apparently relies on threadbare-thin just-in-time inventory stocking for essentials, like personal protective equipment, to a far greater extent than most of us imagined. The shortages of PPE this early in the pandemic response, along with woefully inadequate diagnostic testing in too many parts of the country, are deeply troubling at this late date of Mar. 26. Why in the world didn’t we scale up manufacturing starting Feb. 1, when the alarm bells were clear from China. Or how about Mar. 1, when it was abundantly clear we had uncontained community transmission in the Seattle area for the preceding six weeks? The federal government’s denial, incompetence, short-term thinking, and outright dangerous lies — it’s a nightmare beyond even my darkest fears from the past few years.
I’ve spoken with doctors and nurses. The fear in their voices is palpable. They know this virus is highly contagious. They know it sends about 15-20 percent of people who get it to the hospital. Many patients need ventilators which we don’t have. Where in the world are all these patients going to go to get the adequate first-world care they need to survive?
How far do we have to go to catch up? Forgive the crude table below, which includes data compiled by OECD on hospital beds per 1000 people, through 2017. You have to scroll a long way down to find the United States.
The United States ranks No. 32 in the world, with fewer than 3 hospital beds per 1,000 people (below countries like Italy and Spain, which have been overwhelmed).
Beds are something of a proxy for hospital capacity. Now, you might say, beds can be obtained and rolled out in surge hospitals like the Javits Center in New York. Sure. But even if beds are installed, who will tend to the patients? Anyone familiar with unionization drives for nurses over the past 10 years knows that they are being run ragged and overscheduled, even in normal times. We don’t have a deep bench of reserves to call up. If these frontline workers start getting sick, we simply won’t have enough skilled people to provide care. (See table below from Kaiser Family Foundation, based on OECD data).
Dashboards to Help You Keep Up (Which You Probably Already Have)
The New York Times has a nice visualization of the US map, along with new cases, and deaths, reported on a daily basis. (NYT Latest Map and Case Count). The NYT, given its resources, should lead the US media. It has been simply superb in its overall team coverage.
Johns Hopkins University is a go-to source for worldwide case counts, and deaths, updated in real-time. Sadly, you can see the US moving up to the top of the list, surpassing China as of Mar. 26, in terms of total number of confirmed cases. (Johns Hopkins dashboard).
Covidactnow.org is an excellent resource that provides colorful state-by-state projections of what various scenarios look like, with aggressive community mitigation and without. (H/t to TR subscriber Steve Dickman of CBT Advisors for sharing).
Covidly.com. A simple display. US is now No. 1 in the world in terms of confirmed cases.
Sad, but Predictable Fallout
Eli Lilly announced something that should have been pretty easy to anticipate a couple weeks ago. Clinical trial activity is being curtailed during the COVID19 pandemic. New trials in the queue aren’t being started. Enrollment of new patients in existing trials, are being paused. Existing patients in trials who need to stay on protocol as part of their care plan, will maintain continuity on study. I’d watch for more shoes like this to drop in coming weeks.
Silver-lining Department
Scientists, doctors and nurses will be the new heroes in our society in the 2020s and beyond.
A few highlights from the world of science:
Seattle is a few weeks ahead of the rest of country in the coronavirus outbreak. The Seattle Flu Study, which was set up as a $20 million project to gather samples from people suffering flu-like symptoms in the community to better understand that virus, has been nimbly, and heroically, repurposed to evaluate the community spread of SARS-CoV-2. These scientists from the University of Washington and Fred Hutch have not only provided a crucial set of data-driven warnings to scientists around the US, they’ve turned virology labs into a high-volume testing center when the federal government failed to keep up with a virus that spreads with exponential speed. Read about the Seattle team’s new research plan here.
A brute force team of scientists led by the famous drug hunter Kevan Shokat at UCSF published what you’d have to call a tour de force of a preprint on BioRxiv. They described their work probing for an Achilles heel in SARS-CoV-2. They found “332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays.” Talk about working with purpose and passion. Who knows where this will lead, but holy mackerel. Read the preprint yourself here.
Scientists in China, alongside US peers, are looking at lightning speed for broadly neutralizing antibodies against SARS-CoV-2. Chinese scientists reported Mar. 25 on an almost incredible 206 broadly neutralizing antibodies against the receptor-binding domain on the virus. Antibodies can provide exquisite specificity to a target. The Chinese team reported surprisingly little cross-reactivity with SARS and MERS. But one challenge with antibodies is they are difficult to scale up for all-out mass production quickly. If these go anywhere, antibodies in beginning small batches could be an especially important tool for treatment of patients in severe distress, and potentially for prophylaxis of healthcare workers on the front line. That would be an interim step before we get a cheap, effective vaccine that can be given worldwide.
Disease modelers at Imperial College London rocked the world with their original report on Mar. 16 that as many as 2.2 million people in the US could die from COVID19 in a worst-case scenario. Some skeptics wondered if this was alarmism, given the thin gruel of actual hard testing data that the modelers had to work with in order to make their projections, including the crucially-important Case Fatality Rate. Data on hospitalization rates, similarly, is hard to pin down with sweeping, and accurate, testing data. Even so, a lot more data has come in worldwide in the last 10 days. Now the Imperial College London team is out with a new report on Mar. 26. The updated report expects 7 billion infections and 40 million deaths worldwide this year with no interventions. Mitigation strategies could cut the death toll in half, but would still result in overwhelmed healthcare systems. (Full Mar. 26 report here).
COVID-19 Reading from Around the Web
TR Coverage of the Pandemic (Free & shareable with friends, family & colleagues)
Tweetworthy
Craig Spencer is a physician in New York City. Healthcare workers there are in serious trouble. The wave of COVID19 patients is coming to parts of the US, too.
Read this tweet, which sums up this disastrous state of affairs, and boils with frustration.
In Other News…
Deals
Redwood City, Calif.-based Codexis formed a partnership with Takeda to make novel enzyme sequences for use in gene therapy preclinical development. Terms not disclosed.
South San Francisco-based CytomX Therapeutics pocketed an $80 million upfront payment from Astellas to co-develop bispecific antibody treatments for cancer.
Pfizer partnered with Germany-based BioNTech to work on an mRNA-based Covid-19 vaccine. Plans to work out financing terms will get worked out later, given the urgent need. Cambridge, Mass.-based Moderna staked out a lead in the category, dosing the first patient in a healthy volunteers trial in Seattle, the epicenter of outbreak in the US.
Data That Mattered
Genentech and AbbVie reported that venetoclax (Venclexta) improved overall survival time, in combo with azacitadine, compared with the standard chemo, in a Phase III trial of patients with acute myeloid leukemia. Details coming at a future medical meeting (whenever they might be held again).
Financings
South San Francisco-based Lyell Immunopharma raised $492 million in a Series C equity financing that included 10 investors, according to a regulatory filing with the SEC. The company didn’t issue a press release on the financing, but Bob Nelsen of Arch Venture Partners confirmed to me that Arch participated, and has plans to continue with three large financings in coming weeks, despite the pandemic. Lyell is led by CEO Rick Klausner, a former director of the National Cancer Institute and a co-founder of Juno Therapeutics.
South San Francisco-based CERo Therapeutics raised $40 million in a Series A financing. The company is working on engineered T cells for solid tumors. Arch Venture Partners participated. (See TR coverage on T cells for solid tumors, March 2020). CERo also said it struck a partnership with Lyell Immunopharma.
San Diego-based Design Therapeutics raised $45 million in a Series A financing led by SR One. The plan is to work on nucleotide repeat disorders, starting with Friedreich’s ataxia.
Menlo Park, Calif.-based ReCode Therapeutics secured an $80 million Series A financing, co-led by OrbiMed Advisors and Colt Ventures. The company pools some assets for mRNA and tRNA therapeutic development for lung diseases, starting with primary ciliary dyskinesia and cystic fibrosis.
Emeryville, Calif.-based Eureka Therapeutics raised a $45 million Series E financing to advance its cancer treatment programs. Lyell Immunopharma led.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Amanda Banks Christini, MD; CEO, Blackfynn
Yesterday I woke up on an island.
I am temporarily – but purposefully — isolating myself and my two children, ages 10 and 12, in a familiar place that carries with it a slower rhythm from a different time. It’s our second home.
It also happens that, on the first day of spring, there are still no cases of suspected or confirmed COVID-19 on this island. Talk about isolation.
A week ago, I left Philadelphia to come here for the safety of my family.
But I didn’t leave our communities, or our world, behind. I’ve decided to come back, and put my medical training to work on the front lines during this time of urgent need.
We are all struggling with, distracted by, this new reality that has been thrust upon us by the completely predictable intersection of a rapidly transmissible, emerging infectious disease and a fatally neglected public health infrastructure.
Our current administration is adding fuel to this fire through characteristic and striking ignorance. The administration’s actions — and inaction — will have profound long-term effects on our fragile healthcare system and on our economy. But while the temptation to place all the blame at the feet of elected officials is strong, we are in this situation because of many decades of broken policies and misplaced investment.
I am angry and frustrated. But I don’t have time for this now, because I am consumed by the balance between being a CEO of a company with 36 employees, a mother, a daughter, a sister, a friend, and, a practicing internal medicine physician who also works as a hospitalist in Philadelphia to care for acutely ill inpatients.
I am profoundly wrestling with the obligations of these roles, which, in this new reality, can be both fully aligned and simultaneously in stark conflict.
I have a fiduciary duty, as CEO, to not take undue risks as a “key person” at my company. But the healthcare system will collapse under the weight of this pandemic if healthcare workers don’t step up. And they are stepping up in droves, despite the lack of supplies. My employees need decisive leadership. They also seek my medical advice at a time when the mixed messages of state and federal officials, combined with certain media outlets with irresponsible tendencies and partisan biases, is deafening. It’s hard to know what to believe. I am balancing my passionate dedication to patients with a fierce instinct to protect my children.
I jumped on the front lines in 2014 as a first responder against Ebola and was a (pregnant) medical resident taking care of patients with H1N1 flu in 2009. I will not sit on the sidelines and watch my colleagues fight this battle.
In the end, despite the risk I know it will pose to me and possibly my kids, I will have to leave the temporary isolation of my island retreat. I will have to make arrangements for child care, and then go to the front lines. I need to help care for not just patients with COVID-19 infection, but also for the many patients with heart failure exacerbations, complications of uncontrolled diabetes and hypertension, renal disease, heart attacks and strokes who are admitted in greater numbers because their routine clinic visits have been cancelled to make way for the surge of pandemic victims in dire need. We are going to see a chain reaction of more sickness in these patients, because they won’t get adequate telemedicine consults. That’s because this country has never prioritized, nor authorized reimbursement for, telemedicine services.
As CEO I made the decision, like many others, to make working remotely mandatory. I am trying to keep a company of now fully remote workers engaged, productive, motivated and safe – a company that I co-founded, that I lead, to which I am passionately dedicated. The employees are people to whom I am deeply connected and feel a tremendous responsibility. In a world where the financial markets went from soaring to reactive, trepidatious and emotional, I am also trying to steer our company through an unprecedented time, at a moment when we were, and are, poised to do great things to impact patients.
We all have our version of this struggle. We are all some combination of parents, kids, friends, leaders, colleagues. We will redefine what social engagement means. We will find new ways to fulfill our need for community. We will get sick, and help others get well. Realistically, some of us will die.
But, as a community, a nation, and a world, we will get through this. I can only hope that when we do, we indeed come through to the other side stronger.
I implore everyone to learn from this unprecedented moment in history; in a nation so fundamentally short-sighted and focused on the value of the individual, can we become a country with a longer view? One informed by science, epidemiology and the value of basic principles of public health? The decision is ours: as a world, as a nation, as a community, but also as individuals.
I do not have the answers. I can – we all can – ask questions. Today, I am back in Philadelphia preparing to go on service on nights and weekends to treat patients. This is my contribution.
We must all contribute in our own way: Don’t hide. Don’t let fear paralyze you: find facts and resist the noise. Be kind to each other. Find empathy. Resist hoarding food and supplies — especially masks that medical workers and people on the front lines desperately need and are in dangerously short supply. Build virtual communities. Support a friend or coworker or family member who is alone and at risk.
And vote. Especially, vote.
Together we can use this remarkable moment to catalyze the change our nation and our world so desperately needs. The time is now.
What will you do?
David Shaywitz
The current crisis represents a potentially defining moment for at least some health technologies and technology-enabled services.
Telehealth, as discussed in my last column, is one conspicuous example, and the jury is still out. The potential benefit seems especially striking at a time when so many Americans are being told to stay at home, yet there are also serious concerns, both short-term (can existing telehealth capabilities adapt to exploding demand?), and longer-term (including not only a thicket of regulatory and reimbursement hurdles, but also challenges around data governance and trust).
Nevertheless, as Dr. Joseph Kvedar, VP of Connected Health at Partners HealthCare puts it, “telehealth is clearly making the case for how technology should be used to imagine how care and services are delivered. I believe that there will be no turning back.”
The corresponding example from the pharma world might be the use of technology to enable remote trials. It’s an urgent consideration in light of the pandemic, which is having a predictably negative impact on clinical trials. In the last 24 hours, Lilly announced it would “delay most new study starts and pause enrollment in most ongoing studies,” while “continuing ongoing clinical trials for patients who are already enrolled.” Meanwhile, the New York Times reports BMS has told researchers “it will put off beginning new clinical trials for at least three weeks,” “will not initiate any new sites for clinical trials until April 13” (or later), and said “studies involving healthy volunteers should be paused if they are at a natural break point until at least April 13.”
Clinical trials, like much of clinical medicine, have historically focused around global networks of brick-and-mortar centers. These centers can be stand-alone facilities, which are typical for early phase, highly monitored studies. They can also exist in large medical centers with physicians who have agreed to participate in the study. That model is quite common for larger, mid- and late-phase studies.
While operating in a site-focused fashion enables a relatively high degree of process control, it also means that studies are generally limited to subjects who can show up to a single location, often repeatedly over days, weeks, and typically months. The convenience challenge is often cited as a major reason why participation in clinical trials is so abysmally low.
This matters for many reasons: a key hurdle for clinical studies is it often really difficult to find enough patients to study, a persistent challenge which adds significantly to the length and cost of trials.It also means that many potential subjects never have the opportunity to participate because they are not located near a trial site and/or the time and travel commitments are prohibitive.
Estimates vary for just how small the percentage of eligible patients who participate in trials is. Some suggest the figure is as low as 2%; a recent study led by Joseph Unger of the Fred Hutchinson Cancer Research Center and focused on cancer patients puts the number at 8%. Foremost among the factors cited for low participation by Unger and his co-authors is that “a trial may not be available where the patient is being treated.” As they point out, “Having to travel to participate in a trial can be an overwhelming burden to patients.”
Driven by these widely recognized needs, there has been profound interest in finding ways to increase the reach of clinical trials, which often involve the idea of the trial going to the patient, rather than the patient going to the trial. This was the driving force for Novartis to ink a high-profile deal with the remote trial company Science37 in 2018, a pact aiming to deliver 10 studies in three years (our TechTonics episode with Science37 co-founder and former-CEO Noah Craft, who stepped down in 2019, is here).
As the Novartis press release put it, “Decentralized, or virtual, trials harness digital technology to allow some or all aspects of a clinical trial to be carried out at a participant’s home or local physician’s office, rather than at a central trial site such as a large hospital…”
Improving the diversity of participants is another attraction of virtual approaches. As a Novartis executive says in the same statement, “Remote participation in research has the benefit of improving the breadth of participation from wider community and socio-economic backgrounds, while also allowing us to gather more meaningful real-world evidence in our clinical trials.”
In theory, a company that had an established, decentralized trial capability might be more robust to site-focused challenges like those associated with the pandemic. Certainly, the FDA’s recent guidance makes clear it is receptive, under the conditions of the pandemic, to remote approaches as supportive of participant safety.
The guidance document specifically encourages sponsors to consider “alternative methods for safety assessments” such as “phone contact, virtual visit, alternative location for assessment,” and presses sponsors to “determine if in-person visits are necessary to fully assure the safety of trial participants.”
The Agency goes on to note that depending on the circumstances, some “investigational products that are normally administered in a health care setting” might be given some other way (“e.g. home nursing or alternative sites by trained by non-study personnel”). The Agency even suggested the possibility of “the use of virtual assessments” for efficacy evaluations. Collectively, the document at a minimum highlights the potential of a remote clinical trial capability, which would seem useful in the context of this crisis.
My best guess, however, is that remote trial monitoring is still such an emerging capability that few, if any, pharmas have it available as a ready substitute for in-person visits; this may not even be appropriate for many study protocols. Some experts such as Andrew Matzkin, a partner at the consultancy Health Advances, believe that decentralized clinical trials may be a promising concept that could work technologically, but still need to provide more evidence, demonstrate real world usability, establish credibility, and describe a reliable path to commercial scale before they’re likely to gain general acceptance.
Perhaps for a few very high priority trials that are already underway, pharmas are likely to do every possible thing they can to keep these studies advancing. Pharma companies will try to use remote capabilities and deployed specialists to perform the necessary evaluations, assessments, and (where required) dosing. Especially at a time when health systems and healthcare workers are already so overwhelmed, any success from this approach is likely to be extremely limited.
At times of crisis, it’s often said that the startups that benefit the most aren’t those that are formed in the heat of the moment to address the emergent needs, but rather those that were created years back, and are poised, for lack of a more tasteful term, to take advantage of the moment.
Two startups in this space are Evidation Health and Koneksa Health, which both offer flavors of what might be called “digital tool enablement as a service.” While neither seem positioned to save pharma from the trial continuity crisis, the value of their capabilities is likely to be evaluated and recognized at this moment.
Evidation Health, led by Deb Kilpatrick (her TechTonics episode here), is perhaps best known in recent days for its partnership in the “Heartline” 150,000 person study – “a big deal of digital health” according to CNBC’s Chrissy Farr – recently launched by J&J and Apple. Heartline’s website says Evidation “provides the technology and study operations that enable the Heartline app and study experience for participants.” Their role, Kilpatrick says, is as the “software-based virtual site,” explaining that Evidation’s research platform enables a contemporary, decentralized research experience for older adults mediated entirely through the iPhone while collecting and processing their (explicitly consented) research data.
Evidation believes its secret sauce is gleaning insight from the data generated by these digital tools – information the company refers to as “person-generated health data, or PGHD), a distinctly non-trivial task accomplished by the data science team build by co-founder Luca Foschini. Evidation’s approach has been used in studies of the flu, as well in a recently-launched longitudinal program seeking to better understand the perceptions, experience, and health of Americans in response to the pandemic; using its already-deployed patient engagement app called Achievement, the company hopes to integrate surveys and digital measurements from users who opt-in; as of March 18, over 100,000 people apparently had.
If Evidation’s focus is obtaining meaningful clinical insights by analyzing what it would describe as high-quality, person-generated health data from consumer devices and engagement apps, Koneksa Health is especially focused on the validation of remote measures for use in traditional clinical trials, and supporting pharma stakeholders who make go/no-go decisions, as well as the regulatory authorities who must accept digital measures in place of, or in addition to, the current gold standard. (My simple-minded dichotomy sees Koneksa focused on pre-approval trials, and Evidation capturing value from post-approval studies and other research; in reality, the capabilities of these two companies presumably overlap).
Koneksa’s focus, says founder and CEO Chris Benko (his TechTonics episode here) is the use of patient-focused digital biomarkers (e.g. remote, device and app based measures of pulmonary function, activity, sleep, vital and hefty signals) to support development of novel therapeutics.”
Benko’s view is that the current crisis, and the FDA’s response, “will require technology tools already designed as fit-for-purpose clinical trial tools,” adding “Koneksa has been deploying tools like this into clinical trials since we launched in 2015.”
Bottom Line: While no company seems poised to save pharma from the clinical trial interruption the pandemic has necessitated, the urgent search for partners with digital capabilities may accelerate the growth of startups like Koneksa and Evidation who are progressively establishing themselves in this nascent and promising space.
Today’s guests on The Long Run are Alexis Borisy and Melanie Nallicheri.
Alexis Borisy, chairman and CEO, EQRx
Alexis is the chairman and CEO of EQRx, and Melanie is the president and chief operating officer.
EQRx is a startup in Cambridge, Massachusetts. It aspires to develop new medicines for serious diseases like cancer. That’s nothing unusual.
What is unusual is that EQRx is seeking to create a company that makes a profit, but does so by churning out many new drugs so it can get by without resorting to the unjustifiable price increases, or outright price-gouging, that has poisoned the reservoir of public trust in the biopharmaceutical industry.
Essentially, it wants to develop and sell lots of innovative drugs at low prices.
EQRx is seeking to mitigate technical risk somewhat by pursuing a “fast-follower” strategy in which the underlying target biology is relatively well-known, and it can learn and quickly adapt to development plans laid out by trailblazers in a new therapeutic category.
By reducing technical risk as a fast-follower, EQRx believes it can run faster, cheaper, lean and mean clinical trials with a higher probability of success. That would reduce its R&D spending and opportunity cost. If it can pull this off several times in a row, the diversified portfolio should give it the flexibility to price its ultimate products a lot cheaper. That’s the thinking.
Melanie Nallicheri, president and COO, EQRx
You might be skeptical. Plenty of people are. Drug pricing has been so dysfunctional for so long. So many vulnerable people in our society have felt exploited and gouged and ripped off for so long. They flat-out don’t trust the biopharmaceutical industry. The public has good reason to be skeptical.
There’s a lot here to think about, in terms of how pharma can and should operate, whether you agree or disagree with what Alexis and Melanie have in mind. It’s worth re-thinking especially in this new moment of crisis and collective spirit during the global pandemic.
I hope you enjoy this conversation.
Please join me and Alexis Borisy and Melanie Nallicheri on The Long Run.
Otello Stampacchia, founder, Omega Funds (illustration by Praveen Tipirneni)
Like most of you, I have been obsessively following “the virus.”
It is having a devastating impact on human life, hospital systems, governments and economies. The worst is still to come, based on what we know about this new coronavirus and its ability to spread with exponential force.
Here are some thoughts on the difficult choices laying ahead.
Before I start, here’s a little on where I’m coming from. I have the dubious advantages of being at the same time Italian-born and a US-based venture capitalist active in healthcare. This gives me a lens into the government, healthcare and culture of a country that has been decimated, and an insider’s view into the scientific community and its prospects for counterattack (mainly therapeutics in my case). As an investor in public and private markets, math is part of the job, and I have a somehow intuitive feeling about exponential growth rates. Please refer to two previous articles on Timmerman Report, warning of the upcoming disaster on Mar. 10, and then on Mar. 18.
As with most (all?) of you, I am watching the daily avalanche of terrible news and the public / policy responses trying to catch up to the inexorable progression of the virus. Note the use of the words “catch up” here, they will come in handy later.
In the US, we went from 89 confirmed cases on March 1 to ~41,000 as I write on the afternoon of March 23 (source: www.worldometers.info/coronavirus). The US, so far, has lagged far behind other countries’ in testing capacity and administrations, so it is catching up there as well. A patchwork of local, state and federal measures are being implemented across the country to try to limit the spread of the disease and preserve hospital capacity (and healthcare workers’ safety).
The economic fallout (at least the initial one) is also becoming starkly evident. Starting in late February, US stock market indices have to date lost ~$12 Trillion (herein shortened to “T”) in market value, or roughly 25-30% from their pre-crisis peak (I will strive to be roughly accurate versus precisely wrong throughout this article).
More importantly, entire sectors of the economy (employing a huge portion of the US workforce) are veering rapidly towards bankruptcy: the lethal combination of lack of demand and restrictions on movement has made their business no longer viable (in these circumstances). Hotels, restaurants, airlines, gyms, physical therapists, etc etc are making millions of people redundant across the board.
The US lacks (for the time being) social safety nets that are much more prevalent in other countries. That increases the severity and amplitude of these kind of shocks. The US economy generates about~$40T per year in gross domestic product. Of that, ~70% is composed of services and consumers’ consumption. It is painfully obvious to see how broadening, enforcing and / or continuing “shelter at home” policies in the US for a much longer period will cause incalculable economic damage. The chief of the St Louis Fed was quoted recently saying unemployment in the US could reach 30% in Q2 2020, and GDP could go down by ~50%. This is equivalent to what happened to the US economy during the Great Depression of late 1929 and through the 1930s, and it is happening at a much faster pace – a matter of weeks.
In this context, I see / hear / read a number of voices arguing for a “let it rip” strategy: i.e., continue “life as normal,” spreading the contagion without any radical social distancing measures, accepting that there will be a (slight?) increase in the number of casualties but preserving the broad health of the economy. This virus has a mortality rate of close to, and quite possibly, lower than 1%. On Mar. 16, disease modelers at Imperial College London, factoring in the best available estimates at the time, estimated that the novel coronavirus would kill about 2.2 million people in the US alone under what you could call a “let it rip” strategy – one that doesn’t utilize the disruptive social distancing interventions currently being imposed. A day later, Mar. 17, Stanford University epidemiologist John Ioannidis argued that “we are making decisions without reliable data.”
One of the basic arguments underlying the “let it rip” strategy appears to be the Precautionary Principle: “The precautionary principle (or precautionary approach) is a strategy for approaching issues of potential harm when extensive scientific knowledge on the matter is lacking. It emphasizes caution, pausing and review before leaping into new innovations that may prove disastrous.” (Wikipedia).
Spoiler alert: this discussion is based on fundamental flawed assumptions, at many levels. The (strongly worded, high conviction, HIGHLY evidence-supported) response to this “argument” should be: “(expletive removed) no!” If you carefully, cautiously wait for all the data to come in, your actions will come way too late. Also, interestingly enough, I will end up using the same Principle to argue exactly the opposite of the proponents of “let it rip.”
Now please bear with me as I try to discuss in some tedious detail why this is the case.
The Importance of R0 and Some Exponential Growth Rate Basics:
R0 (or R “naught”) is a measure of how many people one person infects. R0 = 0 (if you are by yourself on a desert island) means you will not infect anybody during the course of your infection; R0 = 1, means you will only infect one person. R0 = 3 means (ah, ok, I see that you got it by now).
For the sake of comparison, “normal” seasonal flu is considered to have an R0 of ~1.3-1.4. Coronavirus is considered to have an R0 of ~2.5-3.0. You REALLY want R0 to go below 1 to contain a pandemic. Importantly, in addition to depending on the virus’ infectivity, incubation period etc etc, R0 is ALSO LARGELY DEPENDENT ON PHYSICAL PROXIMITY. Simply put, if you have a highly contagious (possibly asymptomatic) Italian carrier in an Italian bar in Milan, every bar customer (and almost every surface) will be covered with virus by the time it takes to finish an aperitivo (kind of kidding, but kind of not kidding).
Now, let’s assume the coronavirus average infection cycle is ~4 days (meaning one person infects an R0 nr of people every 4 days). This is where problems start with exponential growth rates. What happens with 10 cycles following the initial infection(s) caused by that person: 10 incremental infection cycles (~1.5 months): normal seasonal flu (R0: 1.4): ~29 people infected. Coronavirus (R0: 3.0): ~59,000 people infected. That means one asymptomatic person, in this coronavirus season, leads to the infection of another FIFTY NINE THOUSAND (I thought that deserved all caps).
Professor Hugh Montgomery, Director of the University College London Center Institute for Human Health and Performance explains this really well (and with a better British accent that I could ever muster) in an interview with Channel 4 here.
The Problem is Hospital Capacity:
Again, please read the previous articles published on this topic on Timmerman Report from Mar. 10 and Mar. 18.
Basically, the important argument behind the “let it rip” approach is that a 1% fatality rate is a price (steep, but worth paying I guess?) for maintaining a functioning economy and not lose ~$1T / month in US GDP. We also do not know enough about the virus mortality rate, natural immunity etc etc so we should not “rush to judgment.”
I am not going to dignify the “natural / herd immunity” argument (there is no natural / herd immunity against the virus: it is a NEW VIRUS that no human on this planet has been exposed to before). What we know today about it is dwarfed by what we still need to learn.
First fallacy: consumption / economic activity will continue as “normal” should we lift restrictions on movements. I am really not sure how to address that one, unless it relies on the assumption that people are completely ignorant of the fact that there is a pandemic going on, and they’ll instantly snap back to life as normal once social distancing restrictions are lifted. Are you really going to take that trip to Milan for Easter now? Scheduling your wedding with all grandparents attending (knowing 1 in 4 of them will likely die if they get infected)? Assuming you could even board a plane, that is. (Full disclosure: my wife and I HAD a wonderful holiday trip planned to Milan to see my family there for Easter. Obviously, we cancelled).
Second, MASSIVE fallacy: the assumptions behind the 1% mortality rate. This might possibly end up being the “undisturbed” mortality rate, when it is all said and done: meaning, this SHOULD be the mortality rate IF you can obtain proper medical care (hospital bed, sufficient supply of oxygen / drugs if needed, caring and competent nurses and doctors).
Now is probably a good time to make the obvious argument that lean, efficient hospital systems (we are in a capitalist society after all) are not structured to be resilient and provide, additional capacity in a pinch.It is actually extremely expensive for a hospital to have spare capacity in terms of critical care beds, ventilators, nurses, doctors, drugs etc. So, they do not do it. Even countries perceived to be more like “social democracies” than the US do not have nearly enough spare capacity to tackle such a surge in cases. Italy has a very good hospital system. China, notwithstanding popular perception, has an excellent healthcare system, no lack of critical care equipment, and they moved 40,000 doctors into Wuhan’s hospitals to make sure they could cope. They also shut down the city when they had 500 officially diagnosed cases. Still, Italy and Wuhan had mortality rates skyrocket as soon as hospitals were saturated. Any incremental patient who needs oxygen (and cannot be properly tended to) will die. Mortality also greatly increases as hospital infrastructure degrades: you cannot fast track the training and education of new doctors and nurses in a few days. Healthcare workers are toiling under wartime conditions, getting infected themselves and dying. Which further compounds the lack of hospital capacity.
In addition, if hospitals get saturated / overwhelmed: every heart attack can become fatal if ambulances cannot reach you / hospitals cannot administer proper care. The US has ~1.5M heart attacks a year, causing ~500,000 deaths when proper care can be administered. The US has roughly 1.9M new cancer cases per year (source: https://www.cdc.gov/cancer/dcpc/research/articles/cancer_2020.htm). These patients are usually immunocompromised after getting chemotherapy or radiation treatment, which makes them very much at risk from opportunistic infections like this coronavirus. In addition they need urgent, critical treatment to achieve remission. In 2018, 34.2 million Americans (10.5% of the population), had diabetes (source: www.diabetes.org/resources/statistics/statistics-about-diabetes). Apparently, diabetics coronavirus patients have a much higher mortality rate. We don’t really understand why that is yet. The list goes on.
One (scary, but I believe accurate) way to look at this in the US is to check out the website www.covidactnow.org: it simulates by when different US states’ hospitals will be overwhelmed by the number of confirmed cases of infection, depending on how we slow down the virus by using different types of social distancing measures to reduce R0 as much as possible.
As you can see, for a number of places, in particular NY, it is too late already. The number of cases will continue to mount over the next two – three weeks. This is why New York Gov. Andrew Cuomo (I cannot help but appreciate another fellow Italian’s decisive response) has asked for federal assistance, and is trying his best to increase hospital capacity in the city. May the fates be always in his favor as well.
Finally, please read Tomas Pueyo’s insightful blog post on this as well. Conclusions are similar to what you will find herein and in my Timmerman Report from Mar. 10.
Bottom line: “let it rip” is not sustainable. The economic and (more importantly) social cost of the disease is going to be even higher than if we undergo a 3-4 weeks shut down. Assuming even modest degradation of the US healthcare infrastructure, the death toll could rise to much more than 1% of US population (about 329 million people currently, according to the US Census Bureau).
But: We Cannot Have Radical Social Distancing for 18 Months!
True, it is not sustainable to have the global economy on lockdown for 18 months. Most important, people cannot comply with such isolation measures (especially those pesky, frolicking fools celebrating Spring Break in Palm Beach). Absolutely agree on that.
OK, here then are some thoughts (feel free to pass them along your favorite policymakers): in temporal sequence from now:
1. We (the US) need NOW a nationwide, ideally even globally-coordinated, “pause” of 3-4 weeks at a minimum, with as little movement of people as possible, across the entire US. I mean a shut down like Italy, enforced by police etc to make sure these frolicking teen fools in Palm Beach (see above) do not continue spreading the virus; no travel unless absolutely necessary. Note: from the moment you impose and enforce such a lock down, then it takes ~2 weeks for cases and deaths to reach a peak. They will continue going up in the meantime. New York City now is like Milan and could become very soon like Bergamo otherwise. ALSO NOTE: two weeks after you impose such a lockdown, things improve. Italy has now turned the corner: in the last two days, the number of new confirmed cases and most importantly, number of fatalities, is decreasing. The lockdown in Italy started on Mar. 9, exactly two weeks ago.
2. There needs to be absolutely clear and effective communication from the federal government. They need to enlist any traditional media sources and social media (Twitter, Facebook) with a simple, clearly communicated message: Social distancing / stay at home will work to reduce the infection rate; BUT it needs 2-3 weeks to show some results and it NEEDS TO BE ENFORCED. Our social structure and citizen relationship to authority is very different from Asian countries: but this means even more clear communication is absolutely necessary. We need to enroll every citizen in the effort. Make sure supply chains / logistics distribution / food and essential medical equipment manufacturing / energy production / broadband infrastructure can take the strain. All these activities can enroll people otherwise made redundant by the industries most affected.
3. In the meantime, during that pause period:
4. The other stuff (how to make sure workers maintain healthcare insurance), can still survive if tens of millions of people are unemployed starting next week etc. This is way above my pay grade but also super important to make sure we can come out the other side.
We will come out of this. But, the next 6-8 weeks are critical in preserving our hospital infrastructure. The virus spreads way faster than you think. If we delay implementing these measures even a couple days more, the consequences are disastrous. The math is inescapable.
To leave you on a lighter note, and a perhaps more entertaining take on how efficient technocracies should make decisions (versus the dilemmas facing politicians), this video clip from the old British show “Yes, Minister” is priceless. Moral: I hope we can stop listening to other “opinions” and start listening to the science.
Follow Otello Stampacchia on Twitter: @OtelloVC
This article expresses the personal views and perspectives of the author. The views and perspectives expressed here do not necessarily represent the views or perspectives of Omega Fund Management, LLC or any officer, director, partner, member, manager or employee of Omega Fund Management, LLC or any of its affiliated entities.
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David Shaywitz
Crises can serve as catalysts. History has shown they increase the recognition that change is needed, and lower the activation energy required for it to occur.
The COVID-19 crisis has already been widely recognized as potential catalyst for telemedicine, and more generally for the accelerated adoption of digital tools in both clinical medicine and clinical trials. In just the last week, the FDA released urgent new guidance (here, here) seeking to smooth the way for both.
The surprise is: some of the most ardent champions of digital health are thinking critically about the current moment, warning that if we abandon vitally important safeguards in our rush to embrace technologies, the adverse impact on patient trust will poison the field for decades to come. Moreover, they argue, even in a crisis, you don’t need to choose between rapid execution and good data privacy rights – indeed, they suggest, especially in a crisis, we can, should, and must push for both.
***
Telemedicine has long seemed like an application of technology particularly well suited to pragmatic incorporation into care, enabling patients and providers to engage remotely, without the time and aggravation of traveling to a medical office.
In concept, it embodies at least some aspects of the house call, albeit without the laying on of the hands.
Yet, telemedicine long struggled for real traction. Some, like Eric Topol, a thought leader in this area, believe that “[the] past decade saw telemedicine finally cross [the] chasm,” described by Geoffrey Moore, where the adoption of emerging technology moves from a few visionaries to the “early majority of pragmatists,” as Topol and E. Ray Dorsey recently wrote in The Lancet.
Others would surely argue that even if telemedicine hasn’t quite crossed the chasm in most areas, it is at least getting close. But almost everyone agrees that the adoption over the past two decades has been much slower than many had expected.
Why has telemedicine been such a hard sell, especially in an age where consumers routinely use their phones for everything else?
To oversimplify only a bit, a big part of the answer is: incentives. Providers have struggled to get paid for telemedicine, at least at levels comparable with in-person visits. As venture capitalist and health systems expert Bob Kocher says, Medicare requires an in-person visit before a patient can access care virtually, and even then, the reimbursement for a telemedicine visit tends to be relatively low.
My Tech Tonics co-host and digital health guru and investor Lisa Suennen agrees reimbursement is an important issue –“telehealth-provided services needed to be reimbursed the same as the equivalent service provided in person,” she says. As Peter Antall, chief medical officer of telehealth company American Well recently told STAT’s Erin Brodwin, “The reimbursement challenge still exists for telehealth,” a lament echoing the complaints of genetic testing companies a few years back.
Suennen also highlights another challenge: the need for in-state medical licensure adds another wrinkle: a licensed California physician can’t provide telecare in New York — or Nevada, or any other state — unless she is also licensed in each of those states. The burden is therefore on the practitioner – who’s already loaded with responsibilities — to jump through a series of hoops to get licensed in multiple states if they want to create a thriving telemedicine practice. By design, this makes it more difficult for less busy physicians in one state to ease the burden of overwhelmed doctors somewhere else.
An additional hurdle, physician-entrepreneur and telemedicine guru Dr. Seth Feuerstein points out, is “general inertia in a system filled with risk averse folks who have little or no incentive to do things in a better way.”
Add to this the problem of what Kocher calls “clunky technology.” As Suennen points out “some technologies are really good and some aren’t – you need to choose wisely.” (Providers generally need to use technology that is compliant with HIPAA regulations, meaning you can’t just use whatever consumer videochat app you have available.)
Yet another often appreciated challenge is cultural: as one expert pointed out, “some doctors don’t like the loss of control” that might be associated with telemedicine. Suennen says there’s a lot of “provider discomfort” with the idea, and many don’t like being on screen.
Many patients are equally reluctant to change; Kocher cites as another barrier “the lack of demand by patients who are happy with the status quo.” Or as Suennen bluntly puts it, “people still want healthcare mostly from people” rather than videoscreens.
* * *
Enter the COVID-19 crisis, which has changed, at least for the moment a few key factors. Today, both patients and physicians are highly motivated to minimize clinical visits, which intrinsically introduce an increased risk of infection for both physicians and patients – hospitals and clinics are good places to avoid these days, if at all possible.
In addition, some reimbursement and HIPAA barriers have been waived to make it easier for seniors to access telecare, and for physicians to get reimbursed for this – changes that actually unleashed a tidal wave of demand that overwhelmed telehealth providers, according a recent STAT article. (STAT’s coverage of the pandemic in general, and this aspect in particular, has been superb.)
Of course, many of these COVID-19-motivated changes may revert after the pandemic subsides.
On the face of it, the crisis would seem like a transformative opportunity for telehealth (at least once the initial crush of interest is managed). Yet, as I spoke with a number of savvy stakeholders who have been champions of digital health, I was struck by their caution, which seems almost more prominent than their enthusiasm.
The key issue for many, including Andy Coravos, CEO of Elektra Labs, and Eric Perakslis, a Rubenstein fellow at Duke, is precisely the potential of a crisis to drive – and justify – significant change. Both Coravos and Perakslis advocate for the importance of privacy (Coravos prefers the term data governance). They both emphasize that even in a crisis, we must not be lulled into a perceived false choice between speed and privacy (or speed and good governance).
Coravos and Perakslis contend that there are plenty of opportunities to have speed and privacy, and argue we should push citizens and governments to renegotiate for those opportunities. Privacy policies, terms of services, and end-user-license agreements can be re-written during public health emergencies, they suggest, to protect those who are vulnerable. Hospital systems, governments and others purchasing on behalf of those who cannot make these decisions, Coravos and Perakslis emphasize, can and should factor these considerations into their procurement negotiations. (For more on the risks of data governance in telehealth, see this recent opinion piece in STAT by Kirsten Ostherr).
The core issue, Coravos suggests, is trust; for telemedicine and other digital tools to truly gain traction, users need to be able to engage these tools with trust – trust in the fidelity of the measurement, and trust that the data won’t wind up being used, without their permission, to sell them ads (best case), or deny them insurance, a worrisome concern.
For Coravos, the key opportunity of a crisis isn’t to accept the necessity of a false, bad choice — such as supporting public health at the cost of personal privacy — but rather, to use this moment to push for strong governance, so that the tools and approaches developed at this moment of need will earn the trust needed to support their use once the emergency has passed.
A particular concern raised by Perakslis is that, in the context of the crisis, many “people are running in with dubious products and solutions,” adding “lots of dodgy stuff is going on.” Echoing the flavor of concern raised by Coravos, Perakslis adds he’s very worried that “Silicon Valley and the VC world are pushing for relaxation of every basis of regulation and ethics. The harms will be significant, and this could set things back.” In other words, if people don’t trust the system, they won’t willingly participate in the system, especially after the pandemic is over, and perhaps even during the current crisis.
Adds Coravos: “Good regulation is a necessary precondition for innovation because it creates trust in a system.”
Bottom line: The COVID-19 crisis has created a potential breakthrough moment for telemedicine and other digital technologies. But if these aren’t implemented with care, security and good data rights, any short-term benefit is likely to be offset by the corrosion of trust critically required for enthusiastic patient engagement and long-term success.
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