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05 August 2020 02:38

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FOMAT Medical Research is testing an antibody cocktail called REGN-COV2, which has been gaining attention nationally as a possible way to treat and prevent the infection. Anyone who tests negative can qualify for the second study, which is designed for healthy people who are at high risk of infection. "So what's important with vaccines and preventative trials in general is that you have high exposure to the disease." While the world is transfixed by the high-stakes race to develop a COVID-19 vaccine, an equally crucial competition is heating up to produce targeted antibodies that could provide an instant immunity boost against the virus. Clinical trials of these monoclonal antibodies, which could both prevent and treat the disease, are already underway and could produce signs of efficacy in the next few months, perhaps ahead of vaccine trials. "If you were going to put your money down, you would bet that you get the answer with the monoclonal before you get the answer with a vaccine," says Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID).

"Antibodies have the potential to be an important bridge until the vaccine is available," says Ajay Nirula, a vice president at Eli Lilly, one of several large companies investing in them. Likely to be more effective than the repurposed drugs now available, such as remdesivir and dexamethasone, antibodies could protect the highest risk health care workers from becoming infected while also lessening the severity of COVID-19 disease in hospitalized patients. Soon after the pandemic began, researchers in industry and academia began to identify, design, tweak, and conduct lab tests of monoclonal antibodies against SARS-CoV-2, the virus that causes COVID-19. On 29 May, Lilly, working with AbCellera, launched the first human study of a monoclonal antibody—a phase I trial testing its safety and tolerability in hospitalized COVID-19 patients. Other safety trials followed, from Lilly's Chinese partner Junshi Biosciences and Regeneron, which developed a cocktail of three monoclonals that works against Ebola.

Regeneron is now testing the efficacy of its COVID-19 cocktail, which combines a spike antibody from a person who recovered and one from a mouse given the spike protein, in three large-scale, placebo-controlled trials. One treatment study run by the company aims to enroll nearly 2600 hospitalized people with severe COVID-19, whereas another, about half that size, will test the antibodies in infected people with mild or moderate symptoms. Lilly has launched its own trials, including a phase III, placebo-controlled study in 2400 residents or staff of long-term care facilities, run with the help of CoVPN. "We should be able to see an efficacy signal very quickly" from these trials, says Amy Jenkins, who heads the Pandemic Prevention Platform (P3) program at the Defense Advanced Research Projects Agency, which for 2 years has invested in speeding the development of monoclonal antibodies for pandemics. Although Jenkins hesitates to make a firm prediction, she says the November-December time frame is "realistic and conservative." That is likely earlier than any vaccine will prove safe and effective, researchers say."I would be reluctant to say [that] would be any earlier than the end of the year," Fauci said at a press conference about the launch of NIAID's first COVID-19 vaccine trial on 27 July. Regeneron's Christos Kyratsous notes that vaccine trials must wait a few weeks for a person's immune system to develop appropriate responses to shots and further weeks for "the event"—a chance exposure to SARS-CoV-2. In contrast, for the antibody treatment trials, "your event has already happened," Kyratsous says. And in the prevention studies, the household contacts of COVID-19 cases will be much more likely to be exposed than people who typically join a vaccine study. Immunologist Dennis Burton, whose group at Scripps Research has isolated highly potent monoclonal antibodies against SARS-CoV-2 that they hope to move into human studies, says he is optimistic that monoclonals will protect people from infection for months with a single shot. Kyratsous says even if monoclonal antibodies don't beat vaccines to the finish line, they still might have a role to play against COVID-19. Operation Warp Speed, for example, has committed $8 billion to six different COVID-19 vaccines; for monoclonals, the government has invested about $750 million, much of it in Regeneron, which will produce somewhere between 70,000 and 300,000 doses before it even has efficacy data. "Unlike with vaccines, it is hard to project the number of treatment courses that will be available," Woodcock says. Prevention, which would be a single intramuscular shot, requires less product than the intravenous infusions used in treatment, she notes, but the amount needed depends on a person's weight. Jenkins says a key aim of the P3 project, which has provided four groups with $96 million in seed money, has been to develop monoclonal antibodies that can be made by the body itself, instead of in large fermentation tanks. "We think we can bring down the cost of monoclonal antibodies," Jenkins says. Regardless of cost, evidence that monoclonals work as preventives could benefit everyone by giving vaccinemakers a clear sign that antibodies against the surface protein of SARS-CoV-2 are enough to protect a person. "It will be earthshaking to the vaccine field in a positive way," says Myron Cohen of the University of North Carolina, Chapel Hill, who leads testing of monoclonal antibodies for CoVPN.