TThe National Institutes of Health is preparing to launch a “flurry” of large clinical trials to test new approaches to treating Covid-19, according to the agency’s director, in hopes of expanding what is currently a limited arsenal of therapies to help people with disease.
In an interview, NIH Director Francis Collins characterized the studies as “really well-developed and rigorously designed clinical trials.”
Among the trials, he said: studies of antiviral monoclonal antibodies to treat Covid-19 in hospitalized patients and patients who can be treated at home; Drug studies to calm the overreaction of the immune system that the agency has chosen from dozens of approved treatments; and anticoagulant studies in very sick Covid-19 patients to prevent problems caused by blood clots. Those treatment studies will be aware of work the NIH is also doing on vaccines, including the Covid-19 vaccine developed by Moderna Therapeutics.
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Currently, only two medications have been shown to be effective in patients with the disease. In clinical trials, Gilead remdesivir reduced the time it took for patients to recover; dexamethasone, a steroid, prolonged survival in the sickest patients in a UK study
Collins, who has been with the NIH for 27 years before becoming director in 2009, said he has “become obsessed” with the agency’s efforts to test medications as treatments for Covid-19. He compared the tense and urgent effort to test Covid-19 vaccines and treatments to his time at the Human Genome Project, when there was intense competition to deliver results before a private-sector project. He said that the current effort is much more important.
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“No one would die if we didn’t do the genome project on any given day,” said Collins.
Approximately one hundred people across government, academia, and industry have been working to organize large, systematic trials as part of the NIH Acceleration of Therapeutic Interventions and Vaccines (ACTIV) Vaccines effort. The goal of the public-private partnership is to develop a coordinated approach to prioritize and accelerate the development of treatments and vaccines.
The researchers have registered with the US government to start more than 1,200 Covid-19 studies, according to a STAT analysis. But 38% were small, with fewer than 100 patients. That disorganized effort is unlikely to provide clear answers about which treatments work and which treatments don’t. Collins said this is why ACTIV is important. “I think it was just what was needed to keep us from going down a path of small continuous studies and chaos about the results,” Collins said.
The new tests will be part of that effort. Regeneron Pharmaceuticals, which is developing an anti-Covid-19 antibody cocktail and is participating in an NIH trial of using these antibodies for prevention, will not be included in the antibody treatment trial. But Collins said other large drug makers would be included. The decision to participate in the studies rests entirely with the manufacturers, and he said he has no complaints when a company, such as Regeneron or, in the case of vaccines, Pfizer, decides that it can move faster on its own.
Collins also warned that the science around treatments and vaccines is complicated and unpredictable, and requires doing many different things with the knowledge that some will fail. But the only solution, he said, is to do many studies in parallel.
Collins said the NIH has aimed not to duplicate efforts elsewhere, so the United States studied remdesivir but not dexamethasone. However, the NIH, the United Kingdom and the World Health Organization conducted their own randomized studies of hydroxychloroquine in hospitalized patients; They were all negative.
Still, Collins promised that the government will ensure that the trials are conducted rigorously “so that you don’t waste time, money, or people’s willingness to volunteer.” And he promised that despite the need to accelerate vaccine development, there would be no shortcuts.
“We will not publish something, and the FDA will not allow us, that is not safe or effective. That is the end result, ”said Collins. “Even if we arrive empty, I will not tolerate the idea of you taking out something that is really harmful.”
The NIH is also trying to fix another problem: the need for better and faster Covid-19 tests, through a $ 1.5 billion effort called the Rapid Acceleration Diagnostic or RADx initiative, which Collins and colleagues described in a editorial in the New England Journal of Medicine on Wednesday.
Current test technology based on polymerase chain reaction “doesn’t seem to work very well in terms of managing demand when demand starts to rise higher and higher,” Collins said. RADx has decided on a format similar to the “Shark Tank”, in which small startups audition technologies to receive NIH support. The requests come from 600 efforts, of which 27 have entered the shark tank stage; one is preparing to begin efforts to increase manufacturing and clinical validation. Collins said most of these efforts are point-of-care tests.
The goal, he said, is to have an impact soon. Collins said: “We are not going to invest in any evidence that cannot be expanded to sufficient numbers to have an impact in the coming months.”
