Aaron Glatt remembers the first time monoclonal antibodies were used to help COVID patients. It was November 2020, he said, in the first year of the pandemic. South his Nassau infectious disease doctor, Mr Glatt said. Oceanside, New York His patient, an elderly woman, was coughing and weak. But not long after her antibody infusions began, “she made an amazing recovery,” Glatt says. “She started to feel better, her breathing improved. She talked to her the next day and she was fine.”
That happy result could not have happened today. Millions of her COVID patients have been successfully treated with these antibodies over the last two years, but due to the evolution of the virus, now he does not block new variants such as BQ.1. no longer useful. In November, the U.S. Food and Drug Administration rescinded the approval of bebuterobimab, the last of his COVID monoclonal antibodies on the market, leaving nothing available for treatment. Pharmaceutical companies are working to develop the latest version. But whether these drugs will be available in months rather than years depends on whether the FDA accepts fact-finding data collected during laboratory studies rather than large clinical trials. It’s taking
Monoclonal antibodies (mAbs) are an important treatment for millions of people with immune system problems who are at high risk of infection because their bodies do not respond effectively to vaccines. Myron Cohen, an infectious disease expert at the University of North Carolina’s Gillings School of International Public Health, said people such as organ transplant patients and cancer patients being treated with immunosuppressants “have to live normal lives in fear of COVID. I can’t,” he said. mAbs are also important for many people who cannot take Paxlovid antivirals. This is because it interacts poorly with other medications, including drugs for cardiovascular problems and migraines.
To develop mAbs, scientists take immune cells from recovered COVID patients and clone them. Antibodies work by binding to and blocking the spike protein of SARS-CoV-2, the virus that causes COVID. Otherwise, they are used by pathogens to enter cells. This binding capacity and the safety of her mAb have been validated through large-scale clinical trials involving thousands of people in the past.
At a December workshop co-hosted by the FDA and the European Medicines Agency, many scientists argued in favor of a faster testing strategy called immunobridging. The idea is to show that the new mAb neutralizes the current variant in the lab and is at least as good as the old mAb that beat the previous variant. “We can now say that the ability to neutralize SARS-CoV-2 correlates with protection against COVID disease in the real world,” said Robert Carnahan, a microbiologist at Vanderbilt University Medical Center. “We no longer need large-scale human studies to determine whether a new mAb is effective. We just need to show that it has antiviral activity. We can do it in the test tube.” Combining small-scale human studies to rule out safety concerns and computer modeling to establish appropriate dosages, these rapid processes could result in 3 to 5 months, according to industry experts. A new mAb for general availability may be produced within the next few days.
Immune bridges already have an established history in the world of vaccines. FDA regulators routinely use it when evaluating new versions of annual flu vaccinations. This approach was also used to approve COVID boosters, and primary immunization against the disease in younger age groups. This is the first time it has been used to evaluate pharmaceuticals. This method has not been used for other antiviral drugs such as mAbs and Paxlovid. These drugs do not affect the immune response, they attack the virus directly.
One mAb therapy called Evusheld has been approved specifically for pre-exposure protection (called prophylaxis) in people with weakened immune systems. While originally providing long-lasting protection, the current variant has weakened defenses. “Pre-exposure prophylaxis is something that has no alternative,” he says, Glatt. “And this is what worries me most.”
by email to Scientific AmericanAn FDA spokesperson said the agency is similarly concerned and will work with pharmaceutical companies to rapidly develop preventative therapies for immunosuppressed patients. However, the FDA has not clarified when it will decide whether immunocrosslinking experimental data is sufficient for his mAb. Pharmaceutical manufacturers are desperate for answers. Christos Kyratsous, head of infectious disease research at the biotech company Regeneron, said: “Of course, I would like to see it move a little faster in terms of regulatory interactions.” Still, he says, “I’m optimistic that we can get there.”
