Stanford Donors Accelerate COVID-19 Research and Drug Trials
Stanford was one of the first academic medical centers in the country to roll out an FDA-approved test to detect the presence of the SARS-CoV-2 virus—a test that was provided for our own patients and as many as 25 other health-care systems in northern California and around the United States. Researchers here have also introduced a highly accurate blood test to detect antibodies to the virus, which in turn identifies individuals who may be protected against reinfection.
Now, Stanford researchers are leading the way in the discovery and development of much-needed new treatments for COVID-19. And it could not be done without gifts from generous donors—support that has enabled Stanford to act quickly and flexibly to find answers.
“We’ve been really out in front here. We have amazing people in laboratory medicine, and their work has been accelerated because of philanthropy,” says Lloyd Minor, MD, the Carl and Elizabeth Naumann Dean of the Stanford University School of Medicine. “The researchers had the ideas in their lab. But to scale it up rapidly—to get the amount of data they need to satisfy the FDA in order to move effective treatments into general clinical use—we could not have done that without philanthropic support.”
Stanford has been fortunate to have highly engaged supporters who have rallied around the COVID-19 fight. Marieke and Jeffrey Rothschild are one couple who felt strongly that they wanted to help with the effort and to encourage others to pitch in.
“This is a global crisis, and speed matters here. As soon as it became evident that this was going to have such health impacts as well as overall societal disruption, we started looking for a way to make a difference. It seemed to us the most impactful path would be to assist in testing existing drugs—to find out if there is something that could reduce the mortality rate or prevent more serious illness. You can’t sit by and watch something like this unfold without trying to find a way to get involved,” says Jeff, a Silicon Valley entrepreneur who has co-founded several companies and spent 10 years as a vice president of engineering at Facebook.
“Stanford has very great capabilities and I believe they are going to make good decisions. As I don’t have a background in biology or pharmaceuticals, I’m having to trust others to carry this forward. But I have a great deal of confidence in the team at Stanford,” he says.
PRIORITIZING CLINICAL TRIALS FOR PATIENTS WITH MILD SYMPTOMS
While the serious illness and deaths surrounding COVID-19 infection have been devastating to our nation and the world, it has turned out that only roughly 20 percent of people in whom infection has been diagnosed will actually be hospitalized. The majority of people who get sick need treatment outside the hospital setting, and treatments for these outpatients with milder but still contagious infections are what is needed to stem the spread.
“The essence of Jeff and Marieke’s philanthropy is that they gave us a chance to build an infrastructure and deploy it in the context of our first few studies at a time when nobody else would have given us that opportunity.
Early on, Stanford researchers recognized that trajectory, and started to mobilize efforts to find medicines that were not just effective, but safe in reducing the burden of the disease on ambulatory, relatively mild patients—a key group of people that is spreading the disease.
“We were able to teach ourselves and the broader community how to do COVID-19 trials in outpatients. The NIH didn’t teach us how to do that. Industry didn’t teach us how to do that. Philanthropy gave us the resources so we could learn how to do that ourselves. What we were able to get started back in March thanks to the Rothschilds’ gift is precisely how to address the problem we are now facing in July,” says Chaitan Khosla, PhD, professor of chemistry and chemical engineering and the Baker Family Co-Director of Stanford ChEM-H.
Dr. Khosla is the leader of the recently launched Innovative Medicines Accelerator (IMA) at Stanford that was created to quickly translate scientific discovery into new therapies and diagnostics. Plans for the IMA were in place before the COVID-19 pandemic struck, but its sights have become focused on helping faculty test methods to slow the spread of the disease, proving the value of the new initiative.
“The essence of Jeff and Marieke’s philanthropy is that they gave us a chance to build an infrastructure and deploy it in the context of our first few studies at a time when nobody else would have given us that opportunity. And that is why we are grateful to them,” says Dr. Khosla.
REPURPOSING THREE PROMISING DRUGS
Using repurposed therapies provides the advantage of speed and a safety profile that is known. Three clinical trials of existing antiviral drugs are now being conducted at Stanford, targeting people who are newly diagnosed with mild COVID-19 and, fortunately, not sick enough to be hospitalized. The goal is to increase the probability that these patients won’t have to go into the hospital and that recovery time is shortened.
Philanthropy is making these outpatient trials possible, along with the infrastructure needed to learn about the mode of action of the virus:
Interferon Lambda – Lambda is an immunomodulatory agent and broad-spectrum antiviral compound; the clinical trial launched in May. Lambda is well-tolerated and appears to have powerful effects in controlling viruses that cause respiratory illnesses such as influenza and the coronavirus that causes SARS, as well as against other common viruses. The compound has the advantage of stimulating an immune response without increasing inflammation in the digestive tract and lungs. This phase 2 randomized controlled trial among people with mild COVID-19—who have just tested positive for the virus—aims to determine whether the drug can help people recover faster, reduce the risk of transmission of the virus, and lower the risk of hospitalization.
Favipiravir – Favipiravir, an antiviral drug, has been approved to treat COVID-19 in Russia, China, and India and is used to treat influenza in Japan. This is the first time it is being tested in outpatients in the United States. Stanford epidemiologists are enrolling patients in a clinical trial to see if favipiravir is effective in reducing the severity of COVID-19 infection in people who have mild symptoms or who may have no symptoms. Researchers also want to know if favipiravir can halt the shedding of the virus and prevent it from replicating, which could help limit the spread of the coronavirus. Patients are being enrolled who have been recently diagnosed with COVID-19 and are not in the hospital.
Camostat – As the focus of a third outpatient clinical trial beginning soon, the antiviral camostat has been used for more than 25 years in Japan to treat chronic pancreatitis. While there is extensive human safety data, the drug does not have FDA approval, so an investigational new drug (IND) application needed to be filed by Stanford. With the IND approved, researchers can now begin recruiting patients for this trial.
STANFORD COVID-19 CTRU: A PLATFORM FOR DRUG DISCOVERY
The above treatment trials are being conducted in the COVID-19 Clinical Translational Research Unit (COVID-19 CTRU), in safe, very large tents in an outdoor environment. Philanthropy was critical to building this foundational platform and infrastructure—sufficient staff, resources, equipment and supplies, even the electricity to power the tents—and helped establish a robust system for these fully functioning outpatient treatment trials.
Patients who have tested positive are recruited to determine their interest in participating in the studies. This all must be done very rapidly; the patient must be enrolled within 72 hours of testing positive.
“The gifts that we’ve received have allowed us to hire the staff to do that rapid screening and qualifying,” says Bonnie Maldonado, MD, an infectious diseases epidemiologist and professor of pediatrics and of epidemiology and population health.
The process requires a team effort. “Nurses obtain consent and help to examine patients; phlebotomists draw the blood; a coordinator runs the tent; runners take blood samples back and forth to the lab at the main hospital, and others do the data entry. It’s all completely self-contained. It’s a beautiful unit. And I think that’s pretty unique, right now in the U.S. as far as I can tell. I want to give credit to my co-lead Upi Singh, MD, who is running the first trial and really helped with the build-out that made it so functional,” says Dr. Maldonado. Dr. Singh is a professor of infectious diseases and of microbiology and immunology.
Patients are followed for 28 days after they are enrolled, and blood samples are collected and banked for possible future research as investigators identify new ideas for therapies. This dedicated COVID-19 biobank is expected to become an invaluable resource to researchers not just at Stanford, but around the world.
IMPACT ON VULNERABLE POPULATIONS
African American and Hispanic communities are being disproportionately affected by COVID-19, and many of the underlying reasons for that vulnerability are rooted in already existing economic and health disparities. Stanford researchers recognize that our COVID-19 clinical trials must be appropriately designed and represented so the results of the trials reflect the population of patients who are affected by this illness. For that reason, half of the patients we have recruited for our clinical trials have been people of color. A gift from Stanford donor Karla Jurvetson, MD, is designed to help engage high-need populations in the interferon-lambda trial to ensure equity of representation that will lead to better health outcomes.
Much work needs to be done to conduct robust investigations into the basic science and disease mechanisms that drive COVID-19 to make it a manageable disease, and many research projects are planned or underway at Stanford. With the infrastructure to prototype and test new treatments in place, researchers envision expanding efforts to more therapeutic candidates and more outpatient trial sites, including the East Bay, in the coming months.
A newly expanded, state-of-the-art Biosafety Level Three (BSL3) laboratory is nearly complete, which will allow Stanford researchers to safely conduct laboratory studies with the live coronavirus in tissue culture. In turn, these studies will illuminate fundamental aspects of the biology of this virus while also identifying molecules that can be effectively targeted by next-generation therapies.
There are so many ways people can make a difference this year. If you have the ability
to help, help.
The Rothschilds provided a generous gift for the outpatient COVID-19 clinical trials—providing half of the anticipated philanthropy needed to ensure there was enough foundational support to get the trials moving quickly forward. Their gift closed the gap after several other donors had very generously stepped forward, including Frank Quattrone and Denise Foderaro, Omar Qandeel, Ernesto Bertarelli, and Vinod and Neeru Khosla, in addition to several large anonymous donations. In the end, the three trials became reality thanks to these philanthropic gifts.
“I think we’re all going to look back at 2020 and ask ourselves, what did we do? And I think it will be uncomfortable if you recognize that you could have done something and didn’t. This is going to be a watershed year,” says Jeff, in a statement that seems to encapsulate his and Marieke’s approach to philanthropy writ large.
“You know the old question where the child asks, ‘Dad, what did you do in the war?’ Well, this is our war. There are so many ways people can make a difference this year. If you have the ability to help, help.”