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New data from phase 3 trials of monoclonal antibodies for patients with recent COVID-19 diagnoses, or at high risk for SARS-CoV-2 infection, could move the needle on clinician acceptance of the treatments, experts say.
Two monoclonal antibody formulations, Eli Lilly's bamlanivimab and Regeneron's cocktail of two antibodies, casirivimab and imdevimab, received emergency use authorizations from the US Food and Drug Administration in November to treat mild to moderate COVID-19 in outpatients. But current recommendations from the Infectious Diseases Society of America's COVID-19 treatment and guideline panel, based on data from a phase 2 trial of bamlanivimab, suggest against the routine use of the drug.
Data from phase 3 trials, for which the companies announced topline results in press releases last week, could result in a revision of the IDSA guidelines when published more formally and the committee convenes on the issue again, said Jason C. Gallagher, PharmD, a clinical professor at Temple University's School of Pharmacy and a member of the IDSA panel. It already appears to be encouraging clinician acceptance throughout the country, physicians said.
The new data from Regeneron indicate that people who were recently exposed to SARS-CoV-2 and received its monoclonal antibodies had fewer confirmed infections than people in the trial who received placebo. In Lilly's trial, high-risk patients newly diagnosed with COVID-19 who received a combination of its monoclonal antibodies bamlanivimab and etesevimab had fewer COVID-related hospitalizations and deaths than those who got a placebo.
"It's validating what already looked to be going that way," said Gallagher. "It makes sense that if you give someone passive immunity, it's going to keep them from being admitted." However, he did not want to speak for the IDSA committee before they meet, and noted it would need more information than was provided in the press releases.
Physicians critiqued the results of phase 2 trials of monoclonal antibodies for the quality of the analysis and limited scope of the research. Those early findings were "inherently fragile," Gallagher said, but the results of the phase 3 trials, once published, will provide the most reliable information on the drugs to date.
Regeneron's results came from an exploratory analysis of 409 randomized participants from an ongoing phase 3 trial testing its monoclonal antibodies for the prevention of COVID-19 in people who live with a COVID-19 patient. The company reported a 50% reduction of overall infections in the treatment group compared with placebo. No participants who received the antibody cocktail had symptomatic infections, while eight in the placebo group did.
Lilly's trial included 1035 newly diagnosed, high-risk COVID-19 patients and found a 70% risk reduction for hospitalizations and deaths for those who received the monoclonal antibodies compared with placebo. Of 10 total patients in the study who died, all had received placebo.
The federal government has distributed hundreds of thousands of doses of the monoclonal antibodies to states, which have divided their supply among local healthcare organizations.
As Kevin Dieckhaus, MD, chief of the University of Connecticut Health Center's Division of Infectious Diseases, put it: "I got a phone call that basically said, 'Congratulations, you're getting X number of units of this antibody. Figure out how to use it.' "
Many hospitals have struggled to administer the antibodies. Organizations have often had to dedicate precious real estate within the hospital for infusions in order to minimize the risks of bringing COVID-19-positive patients into a clinic. But even when they're eligible, many people don't want to pursue treatment.
Between November 30 and January 28, the University of Connecticut had only infused 32 patients, despite aggressive recruitment. "It's difficult to implement preventive care when you're feeling ok," Dieckhaus said. "By the time you aren't feeling ok — God forbid — at that point this product is no longer relevant."
When Julio Figueroa, MD, chief of infectious diseases at Louisiana State University Health New Orleans, learned his organization would be receiving a supply of monoclonal antibodies, he knew "we were going to do it, for sure, but we were sort of wondering how much of an effect it was going to have."
As providers "started getting more experienced with the drug in the state and showing, in fact, that it seemed to be working," Figueroa said, "the enthusiasm for it increased pretty dramatically." The LSU system has now delivered "several hundred doses."
There is still plenty of room for improvement in antibody deployment, said Mark Rupp, MD, chief of the Division of Infectious Diseases at the University of Nebraska Medical Center. "I think there are still a lot of questions to be answered with regards to specific subgroups of patients who are most helped by the preparations."
Currently, Rupp's hospital is focused on recruiting people newly diagnosed with COVID-19 who are either 65 years or older, have a BMI of 35 or higher, or have other risk factors such as immunosuppressive conditions or cardiac diseases. The University of Nebraska has had good success with recruitment, he said.
The need for 2- to 3-hour infusions, one of the biggest challenges for the widespread use of monoclonal antibodies, may be ameliorated if the positive results from Regeneron's study, which administered the antibodies via subcutaneous injections, bear out in the full data publication.
But one other obstacle — newly emerging variants of SARS-CoV-2 — remains out of doctors' hands. As new variants become more common, it's unclear how monoclonal antibodies will hold up, Figueroa said.
In a January 26 preprint paper, for example, researchers demonstrated that the SARS-CoV-2 variant that emerged in South Africa was "markedly more resistant" to antibodies in convalescent plasma, and "completely or markedly abolished" the activities of Lilly's bamlanivimab and Regeneron's casirivimab on their own. But Regeneron's imdevimab appeared to retain its function.
These concerns and other questions, like the difference in efficacy between monoclonal antibodies and convalescent plasma, could be addressed by future trials. But more patients will need to participate in research, said Joann Elmore, MD, MPH, of the University of California, Los Angeles, rather than receiving monoclonal antibodies outside of clinical trials.
For now, Figueroa said, monoclonal antibodies look increasingly reliable in patients newly exposed to COVID-19. "As the pandemic continues, and you have a lot of people in high-risk populations who are still not vaccinated, I think this a good stopgap."
Eleanor Cummins is a freelance journalist whose work runs the gamut of science. Her work has appeared in Vox, National Geographic, and The Atlantic.
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Cite this: New COVID-19 Monoclonal Antibody Data Could Shift Clinical Practice - Medscape - Feb 02, 2021.