A vaccine is likely what will stop the new coronavirus, so it's no surprise that the dozens of programs speeding through testing are getting so much attention.
Even at the unprecedented pace vaccines are moving, the first might not be available until next year. And it'll likely take much longer than that for enough people to be vaccinated that the U.S. achieves 'herd immunity,' and can more definitively curb the spread of SARS-CoV-2.
That's why many experts believe the efforts of a group of companies developing antibody drugs are so vital. Regeneron, Eli Lilly, Amgen and Vir Biotechnology are leading an increasingly competitive race to develop therapies that could give people short-term protection from the coronavirus, or help treat those who are exposed or infected. And they could be more potent than the current standard of care, Gilead's antiviral drug remdesivir, which seems to help hasten recovery from COVID-19 but only modestly so.
"These medicines may be the best chance for a meaningful near-term success," former FDA commissioner Scott Gottlieb recently wrote in an op-ed in the Wall Street Journal.
Still, even if successful — which is no guarantee — these injectable biologic drugs won't solve the pandemic. Their effects are temporary, for instance, and manufacturing will also be a challenge.
But many believe there is a good chance that they could get through clinical testing and be available for use before vaccines arrive. In combination with mass testing and tracing measures, they could, then, be a critical tool in helping keep the disease in check.
"Can you turn this into something where we can take the distancing requirements down in a significant way?" said Ronny Gal, a biotech analyst at Bernstein, in an interview.
The first clinical tests of COVID-19 antibodies should start next month. With those trials approaching, BioPharma Dive spoke with the developers of these drugs and some outside observers about what lies ahead.
What are antibody therapies for coronavirus, and how do they work?
When fighting off foreign invaders, our bodies make antibodies specifically produced for the task. The reason vaccines provide such long-lasting protection is they train the immune system to recognize a pathogen, so immune cells remember and are ready to attack the virus when it appears.
Monoclonal antibodies for coronavirus would take the place of the ones our bodies might produce to fight the disease. Specifically engineered to act like coronavirus-fighting immune cells, the manufactured antibodies would be infused into the body to either tamp down an existing infection, or to protect someone who has been exposed to the virus.
This approach has proven effective against infectious diseases before. A major study in the Democratic Republic of the Congo, for instance, showed a cocktail of antibodies developed by Regeneron reduced the risk of death from Ebola compared to two other treatments. That success has fueled hopes of a repeat, both for Regeneron and for other companies, too.
"Antibodies are the treatments that turned out to be most useful for Ebola. That may or may not be the case with coronavirus," said Diane Griffin, a professor of infectious diseases and of neurology at the Johns Hopkins University School of Medicine, in an interview.
"But it at least brings to the fore the possibility that antibodies could be an important component for treatment."
Effectively, these drugs are synthetic versions of the convalescent plasma treatments that rely on antibodies from people who have recovered from infection. But the engineered versions are easier to scale because they're manufactured in vats, rather than from plasma donors.
The biggest problem with antibody treatments, however, is their staying power. Their effects only last as long as the antibodies are alive — likely a month or more. As Gal puts it, "the weakness is that they're not a solution."
Why care about antibodies if vaccines are the real solution?
First, it's risky to count on vaccines being developed at an historic pace — testing normally takes many years — and be an immediate panacea. There are many other uncertainties ahead, too. No vaccine has ever been successfully developed for any type of coronavirus, and the most advanced prospects rely on new, unproven technologies that have never been made at the kind of global scale needed to fight a pandemic.
What's more, some vaccines are only effective for a portion of people. Among the hardest to help are elderly people with weaker immune systems — the kind that are most prone to serious complications from coronavirus disease. Vaccine's effects also take time; they don't kick in immediately.
"We don't know if the vaccines will work, when they will work, or how well they will work," said Vir CEO George Scangos in an interview. "I hope it will be the case, but I don't believe it will be the case that vaccines provide universal protection for everyone."
Vaccines aside, the cupboard of drugs that doctors can use to treat infected patients right now is nearly bare. The only treatments granted emergency use by the FDA thus far are the antiviral remdesivir and the generic malaria pill hydroxychloroquine. But remdesivir must be infused over either 5 or 10 days and has only shown it may help shorten hospital stays for people with severe disease. It's unclear what, if any, benefit hydroxychloroquine has.
Social distancing has, thus far, helped to keep case numbers from rising exponentially and reduce strain on the healthcare system. But some states are already reducing such measures or soon will, and the economic pressure to open has grown by the day. That will likely lead to a spike in new cases or, perhaps, a second wave in the fall, experts predict. There is a huge need for a temporary solution that can help people until a vaccine arrives.
"We need something to bridge that gap," said Andrew Adams, Eli Lilly's chief scientific officer of RNA therapeutics in an interview. Adams also works on antibodies.
Monoclonal antibodies could help. They're being made with well-known technologies that are used to make many marketed drugs for cancer and autoimmune diseases — and have become effective medicines for other infections like respiratory syncytial virus. Their effects kick in immediately, which means that they can be tested in people with live infections quickly.
Select antibodies in development for COVID-19
|Company||Approach||Modifying antibodies?||Target trial start|
|Amgen/Adaptive||Not disclosed||Not disclosed||Not disclosed|
|Eli Lilly/AbCellera/Junshi||Looking at both options||Not disclosed||June|
How would antibody drugs be used?
What makes antibodies unique, compared to vaccines or antiviral drugs, is their potential to both treat and protect against viral infections. They could work as a "short-term preventative" for healthcare workers who are at "exceptionally high risk" of contracting COVID-19, or as a treatment for people who are sick, said Ray Deshaies, Amgen's senior vice president of global research, in an interview.
Proving antibodies can treat patients with existing disease will be much faster and easier than showing a preventive benefit. As with vaccines, antibodies would have to succeed in much longer tests to fully show they can prevent infections. And it's up to the developers to figure out exactly when, in a disease course, the best time is to intervene with an antibody drug.
Scangos, for instance, said Vir plans to test its antibody candidate in multiple scenarios: in people who are either already hospitalized, newly diagnosed with disease but yet to have respiratory problems, or who have just been exposed to the virus.
"How it would be used depends on which one of those" works best, he said.
Would antibodies be for everybody, or only select groups?
The quickest path to success for an antibody is likely through a drug that has to be given intravenously in a hospital or clinic, rather than through an auto-injector a patient could self-administer, said Amgen's Deshaies. They're also complex to manufacture, transport and supply in massive quantities. Taken together, "it's going to be difficult to use them on the general population," he said.
More realistically, antibodies will provide the most value for the people at the highest risk, like healthcare workers or people who are old or immuno-compromised.
The latter group, in particular, might not even be helped by a vaccine or if they are, only after awhile, said Christos Kyratsous, Regeneron's vice president of infectious disease research and viral vector technologies, in an interview. "There is a huge question mark if this population will respond to a vaccine," he said, "so I don't think monoclonal antibodies are just bridging until a vaccine [gets here]."
Still, it's unknown, as of yet, what the real demand will be for antibodies should they succeed and whether they'd be able to meet it. Executives from each four firms said they are manufacturing their drugs "at risk," before it's known whether they'll work. Their capabilities may depend on how large of a dose is needed and whether multiple antibodies are needed in each of them — which would make them harder to produce.
"These factors are clearly going to affect how the product is going to be used," Kyratsous said.
What other challenges do antibodies face?
Bernstein analyst Gal believes there's a good chance antibodies will succeed in clinical trials because multiple efforts are underway using technologies that have produced treatments for other infectious diseases, like Ebola.
The way they work is also "fairly straightforward," he said. Generally speaking, the idea is that an antibody drug will bind to the "spike" protein SARS-CoV-2 uses to crack open cells, and prevent the virus from entering.
But there are reasons to be skeptical. It's still unproven, in humans, whether a drug that binds to the spike protein will protect an infection or stop one from spreading. Even approved antibodies for infectious diseases don't work for everyone — AstraZeneca's (and now Sobi's) RSV drug Synagis, for example, reduces hospitalizations about 50% of the time.
Jen Heemstra, an associate professor of chemistry at Emory University, noted that it's unknown whether engineered antibodies will grab hold of target viral protein "as tightly as planned," in part because of how they're designed and made. Additionally, while an antibody is supposed to temporarily mimic the effects of a vaccine, it's "unlikely to work with that level of efficacy," she said in an interview.
"There is cautious optimism that they will be beneficial in treating the disease," she said. "But that is tempered with a realization that no single therapy is likely to work for all patients and all stages of infection and that there is still much we don't understand about the virus that can undermine even the most well-planned approaches."
Deshaies added one other potentially significant concern: Examples in past research of antibodies "exacerbating" the effects of other members of the coronavirus family. "That's certainly in the back of our minds and the minds of others that are taking this approach," he said.
How do the antibodies being developed differ?
Regeneron, Amgen, Vir and Eli Lilly are each using different methods to screen for and develop their antibodies. And those initial experiments may lead to different types of products: One type of antibody versus a cocktail of two or three, for example, or antibodies designed to mimic the ones our bodies make, versus those that are modified in some way to improve their properties.
These choices come with pros and cons. More antibodies means more ways to attack a pathogen, and account for potential mutations - at the possible cost of not being able to ramp up a dose to higher levels. Modifying an antibody could help it last longer, but make it look more foreign to the immune system, which could lead to potential problems.
Regeneron is going forward with a cocktail of two synthetic versions of natural antibodies, "We don't like messing with a solution that nature has evolved for millions of years," Kyratsous said.
Vir is modifying its antibodies to make their effects last for multiple months, and with at least one of its prospects, making a change in an attempt to boost its effectiveness. Scangos believes fears those changes could lead to potentially deleterious effects are "overblown."
Amgen and Lilly are still thinking through their approaches. "It's something that we continue to discuss all day," Lilly's Adams said. They're each working in tandem with smaller companies — Amgen with Adaptive Biotechnologies, Lilly with AbCellera and Junshi Biosciences.
Regeneron and Lilly plan to start human tests next month. Vir expects to start trials in the summer. Amgen hasn't been as specific. "We're working as fast as we can," Amgen's Deshaies said. But those timelines mean meaningful data will likely be produced by multiple companies by the fall.
Griffin, from Johns Hopkins, cautions each developer to make sure it knows what it has before moving forward at such speed.
"Just be a little bit humble about your antibody and knowing what it does," she said, "and that it's going to be protective rather than make things worse."