How Antibody Drugs May Fill the Covid Treatment Gap

This class of drugs may be the most effective means of reducing the severity of the virus' impact and could be more effective - and readily available - than natural human antibodies from those who have recovered from Covid. JL

Joseph Walker reports in the Wall Street Journal:

Few treatments have been shown to be effective against Covid-19, and even then, only in hospitalized patients. Potential vaccines are months away from completing testing and becoming available to the public. Monoclonal antibodies, a drug from a body’s natural antibody defenses, may be able to give early protection against the coronavirus, ahead of vaccines.The drugs, injected intravenously, have the potential to work soon after someone is infected, stopping the virus before the  need to be hospitalized. (They)  might also prevent infection in healthy people,

A kind of drug that takes a page from a body’s natural antibody defenses may be able to give many people early protection against the coronavirus, ahead of vaccines.

Few treatments so far have been shown to be effective against Covid-19, and even then, only in hospitalized patients. Potential vaccines, meanwhile, are probably months away from completing testing and becoming available to the general public.

Researchers and health officials express hope certain drugs, known as monoclonal antibodies and in testing by companies including Regeneron Pharmaceuticals Inc. REGN -1.85% and Eli Lilly LLY -1.37% & Co., will fill the breach.

“There is a need for safe therapies to be given early in disease and monoclonal antibodies are paramount among them,” said National Institute of Allergy and Infectious Diseases Director Anthony Fauci. “I’m very anxious to see what the results are.”

The drugs, which are injected intravenously or with a short needle, have the potential to work soon after someone is infected and still feeling only slightly sick, stopping the virus in its tracks before the seriously afflicted would need to be hospitalized.

The monoclonal antibodies might also prevent infection in healthy people, though likely only for about a month. If the promise bears out during testing, the drugs could stand in as a type of temporary vaccine for people at high risk of infection, such as nursing-home residents and possibly health-care workers.

“Today if you get Covid, you will have a wave of fear of biblical proportions,” said Myron Cohen, an infectious-disease specialist at the University of North Carolina who is overseeing antibody studies for the NIAID.

“If I can give you a shot and guarantee you I stop the progression of disease, the world changes,” he added.

Among the companies planning to launch antibody studies in people this year are Vir Biotechnology Inc. and partner GlaxoSmithKline PLC, and privately held Adagio Therapeutics Inc. AstraZeneca PLC this month launched a Phase 1 study of an antibody drug it licensed from Vanderbilt University.

Covid-19 clinical trials are now under way for 10 new monoclonal antibodies, known as mAbs in industry jargon, according to the Antibody Society, a professional association of researchers.

The most advanced are already in mid- and late-stage studies in newly diagnosed as well as hospitalized patients, and in people who haven’t yet been infected. If they clear testing, the drugs might be available as soon as early in the fourth quarter, according to Geoffrey Porges, an SVB Leerink LLC analyst.

Early signs are preliminary but positive. Regeneron’s antibody drug both cleared and prevented coronavirus infections in a study in monkeys and hamsters.

Another reason for optimism, infectious disease experts say, is that the antibody drugs developed by Regeneron and the National Institutes of Health were shown to be effective in the Ebola virus.

Yet some researchers who expect antibody drugs to work in clinical trials are skeptical how much real-world impact they would then have.

Doctors may be reluctant to prescribe a brand-new, expensive medication to patients early on in their disease when the drug is most likely to be effective, said Florian Krammer, a microbiologist at the Icahn School of Medicine at Mount Sinai in New York.

“The problem is putting it into practice and when are you going to use them?” said Dr. Krammer. “Are you going to give it to someone who comes in who’s only a little symptomatic? Probably not.”

The drugs would likely be used preventively by those at high risk of infection or severe complications from the disease, such as nursing-home residents and workers, or people exposed to a household member who tested positive for the virus.

Regeneron and Eli Lilly say that even if the drugs work, there won’t be enough to treat everyone because there aren’t enough manufacturing plants able to do the high-tech manufacturing that mAbs require.

Finite supplies will mean that government officials, nonprofit organizations and drugmakers will likely have to come together to set guidelines for who gets the drugs, said Eli Lilly Chief Scientific Officer Dan Skovronsky.

“It’s not a question of cost or working harder or a desire to make it. It’s just the simple math, the number of manufacturing facilities in the world that are available,” he said. “And we can’t stop making cancer drugs or insulin or anything like that.”

Regeneron joined with rival Roche Holding AG this past week to more than triple the manufacturing capacity for its drug, but said the increase probably still won’t be enough to meet demand.

Monoclonal antibodies are human-made cells that latch onto proteins that drive disease.

Their discovery in the 1970s helped give birth to the modern biotechnology industry, and they have been turned into blockbuster treatments for cancer, vision loss and chronic inflammatory diseases.

Doctors and health officials are looking to the drugs to fill a big gap in Covid-19 treatment. The only drugs shown to be effective against the disease are for sick patients well along the course of the disease, not for patients in the early stages of infection.

Vaccines promise to protect people against infection, or at least reduce the severity of a case. The most advanced are just starting late-stage testing. And if they pass muster, there probably won’t be enough initial supplies for many people.

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Regeneron and Lilly executives say the complexities of conducting studies during the pandemic make it difficult to confidently predict when they will have firm answers on which patients respond best to their drugs, if at all.

To quickly enroll patients, the companies have had to predict virus hot spots ahead of time and then work with overworked doctors who may be too overwhelmed to always focus on clinical trials.

“We’re a little bit like storm chasers, but we’re pandemic chasers,” said Regeneron Chief Executive Leonard Schleifer.

Delays getting coronavirus test results for potential study subjects are also complicating enrollment. The delays, of as much as 10 days, wind up disqualifying some patients from studies that require them to be enrolled within three or four days of testing positive.

“If you can’t test people rapidly, that precludes being able to do a study in recently diagnosed people,” said Lilly’s Dr. Skovronsky. “Improved diagnostics is part of the answer to improved therapeutics.”

In August, late-stage studies were launched evaluating Lilly’s lead antibody in hospitalized and nonhospitalized patients, and these could be completed before the end of the year, depending on how quickly patients are enrolled.

Regeneron expects to have the first data from its study of a monoclonal antibody in hospitalized and nonhospitalized patients by the end of September. The company could seek an emergency authorization based on the data if there is a strong indication the drug is blocking the virus.