Crucial therapy combats high risk
Monoclonal antibodies key in COVID-19 fight
First came the sniffles. Guadalupe Ramirez dismissed them as nothing to be worried about. She popped a pill and forgot about them.
Next came the searing back pain. She dismissed that, too. She’d had rheumatoid and osteoarthritis for more than a decade and recovered from a brain tumor in 2018. She was used to pain.
But she called her doctor anyway to report the flare-up and its unusual location along her spine.
Ramirez said she thought the doctor was being silly when she suggested getting a coronavirus test. Ramirez had barely left the house in months. But the test came back positive.
Her doctor became insistent: Get monoclonal antibodies and get them fast.
Although it was nearly an hour’s drive to downtown Houston from her home near Clear Lake, Texas, two days later, on a Wednesday in January, Ramirez made the trip.
It may have saved her life.
“By Saturday, I wanted to go jogging,” said the 55-year-old former probation officer. “I woke up like somebody gave me a happy pill.”
Monoclonal antibodies, which provide extra immune soldiers to help the body fight off COVID-19, are aimed at people such as Ramirez, who are at high risk for serious disease because they will probably have trouble fighting off the virus on their own.
President Donald Trump credited them for quickly restoring him to health when he caught COVID-19 last fall. He called on the government to provide free doses to any high-risk
American who needed one.
As of Wednesday, the government had bought nearly 1 million doses of monoclonals from the two companies that have authorized products, Regeneron and Eli Lilly, and has made them available to 5,800 sites.
Many hospital systems, particularly those in large urban areas, have adopted the drugs. Forty-three percent of the federally funded doses have been used in patients, according to the Department of Health and Human Services. The remaining doses sit on pharmacy shelves.
Last month, the Biden administration announced a $150 million plan to improve access to the drugs, particularly among vulnerable people.
Delivering monoclonal antibodies has been challenging, requiring an extended infusion and an hour of observation, as well as a dedicated space, away from other people who might catch the disease. Many hospitals struggled to set up such infusion centers when they were needed most, in early January at the height of the U.S. pandemic.
Regeneron released trial results showing that its antibodies, called REGEN-COV, can be delivered via four near-simultaneous shots, rather than an extended infusion, which should make the drug easier to deliver.
The drugs, which are safe for most people, have become more accessible, doctors said, and they work well, when a patient or doctor asks for them early enough in the disease course.
“We’re finally getting them into people,” said Daniel Griffin, an infectious disease specialist with New York-based health care provider ProHEALTH.
Getting monoclonals into arms
Several changes have happened since early this year to get more monoclonals into patients, Griffin said.
Most importantly, he said, research has shown that the drugs are effective, helping 80% to 90% of patients who receive them to avoid hospitalization or worse.
“It’s one of those therapies where you don’t need a statistician to tell you it makes a difference,” Griffin said. “You’re seeing a patient 36 hours later, saying, ‘I feel great!’ ”
The Food and Drug Administration allowed health care centers to set up monoclonal antibody infusion centers, so the drugs don’t have to be administered in a busy emergency room.
“These people are at the height of their infectiousness,” Griffin said. “You do not want to sit them in a room, much like an emergency room, with people who are most vulnerable.”
The FDA also allowed in-home infusions, in which trained personnel come to the patient’s home to deliver the drug.
“So now we have multiple avenues of access all allowing you to get therapy within 24 hours of thinking this is something required,” said Griffin, whose health care system provides infusions in a tent next to an emergency room.
The federal government continues to increase the type of sites where the drugs are available, including urgent care facilities, doctor’s offices, nursing homes, assisted living facilities, health centers, correctional facilities and dialysis centers, HHS spokesperson Gretchen Michael said in an email.
Griffin said more research is needed to know whether it makes sense to provide monoclonal antibodies to those with less than the highest risk for severe COVID-19, or whether they can prevent symptoms of “long COVID,” which can linger for months after an infection.
According to the FDA, monoclonal antibodies are recommended to be used in adults who are over 65, immunocompromised, have a body-mass index of 35 or above, chronic kidney disease, diabetes requiring medication or coronary artery disease.
“Everybody in our medical center who (tests positive for the coronavirus) is evaluated for these criteria and immediately contacted,” said William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine in Nashville, Tennessee. “We are assiduous about that.”
Vanderbilt has treated more than 1,400 people with monoclonal antibodies since late last year and cut its hospitalization rate by more than half, Schaffner said.
“We’re really quite convinced that they are keeping people with risk factors for serious disease out of the hospital,” he said.
Give them early
The key to getting monoclonals to work is to get them fast.
“Time is of the essence,” said Howard Huang, medical director of the lung transplant program at Houston Methodist Hospital in Texas. “If you’re combating a virus and trying to inhibit its multiplication, we’re talking about every hour, every day you wait that makes a big, big difference.”
Methodist set up a system to have pharmacists call people right after their diagnosis to encourage and educate them about the drugs’ potential benefits.
Monoclonal antibodies are expected to be useful even as more people are vaccinated, Huang said. Those who are immunocompromised, such as his lung transplant patients, are unlikely to get full protection from vaccines and are at high risk for bad outcomes if they catch COVID-19. There also will be people who decline vaccination, then get sick.
Getting an infusion early in their infection could be lifesaving, he said.
Huang and his colleagues have treated nearly 4,000 patients with monoclonal antibodies, most during Houston’s COVID-19 surge in January. They contribute data to a national consortium that plans to aggregate information to identify who benefited the most from monoclonal antibodies.
Because the drugs, which would normally cost $2,000-$2,500 for a single-dose treatment, are provided for free and widely distributed, monoclonal antibodies should be made rapidly available to anyone at high risk, regardless of their ability to pay, Huang said.
“It’s not something that’s only available to rich and influential people,” he said. “As a society, we need to make sure everybody has equal access to that, especially the underserved population.”
But access remains a problem for many, he said.
The business of monoclonals
Two companies, Lilly and Regeneron, have monoclonals on the market. Regeneron started with its two-drug cocktail, REGEN-COV, and Lilly added a second monoclonal to its original drug, bamlanivimab, to provide more protection against coronavirus variants. Friday, the company announced it would no longer provide bamlanivimab alone.
Although experts warned the variants might make monoclonals less effective, the cocktails have kept that from happening, said Regeneron spokesperson Alexandra Bowie.
“REGEN-COV remains potent against the variants first identified in Brazil, South Africa, New York, California and the U.K.,” she said via email.
The company has delivered about 300,000 doses of REGEN-COV under its initial contract with the U.S. government and is making supply for the second agreement, which will provide at least 750,000 more, Bowie said.
The authors of federal guidelines for use of monoclonals expressed some concern about Lilly’s combination proving less effective against many of the viral variants, though it appears to remain effective against the B.1.1.7 variant first seen in Britain.
GlaxoSmithKline, in collaboration with Vir Biotechnology, submitted a request to the FDA on March 26 for a monoclonal antibody of their own. They hope to receive authorization soon to provide a one-time, two-shot treatment, said Dr. Amanda Peppercorn, vice president of clinical development at GlaxoSmithKline.
The companies believe their antibody will work on its own, regardless of the variants, she said, but are studying it in combination with Lilly’s bamlanivimab in case that proves more effective.
“The pandemic has shown that monoclonal antibodies are a very rapid solution because of their predictable safety and dosage prediction – you can really model out how they’re going to work,” Peppercorn said. “Because they’re part of the human immune system, they’re a very safe type of approach for a pandemic.”
Monoclonal antibodies are similar in theory to convalescent plasma, in which patients are given a blood product from people who have recovered from the disease. Unfortunately, people infected with COVID-19 seem to make vastly different levels of antibodies, Peppercorn said, so although some doses of convalescent plasma may be useful, it has not proved effective overall.
By contrast, monoclonal antibodies, which originate in recovered patients, are selected for potency, she said, and they deliver a consistent dose.
GSK and the other companies are testing monoclonal antibodies as a prophylactic therapy, to prevent infections in people who have been exposed to the virus and are at high risk for severe disease.
Monoclonals provide protection for about three months.
Adagio, a biotechnology company based in Massachusetts, is developing a monoclonal it hopes will protect people for at least six months and launched clinical trials.
Its drug uses a different target on the coronavirus that causes COVID-19, which Adagio expects will be useful against variants as well as other coronaviruses, said company CEO and cofounder Tillman Gerngross. Its antibody, called ADG20, is more potent and could be administered via a single shot, rather than an infusion or a multipleshot regimen, he said.
The company expects to submit a request for authorization to the FDA late this year.
Guadalupe Ramirez remains a big fan of monoclonal antibodies. She wants everyone at risk for severe COVID-19 to learn about and get them.
“Whatever is in this medication has kept people going. I don’t know what it does, but you’re good,” she said. “The thing is to try it right away.”
“Time is of the essence. If you’re combating a virus and trying to inhibit its multiplication, we’re talking about every hour, every day you wait that makes a big, big difference.” Howard Huang Medical director of the lung transplant program at Houston Methodist Hospital in Texas