Covid-19 Variants Could Make Antibody Drugs Less Effective
When the pandemic first hit, drugmakers raced to find a Covid-19 treatment in the blood of people who had recovered from the virus. They were looking for antibodies — special immune cells that the body makes in response to an infection — capable of neutralizing the virus.
Many scientists thought these antibodies represented the best shot at treating Covid-19 patients. Companies including Eli Lilly, GlaxoSmithKline, and Regeneron identified several of these antibodies, brewed up concentrated versions of them, and quickly began testing them in clinical trials last year. But now, signs suggest that they won’t work as well against new variants of the virus.
Known as monoclonal antibodies, the drugs mimic the body’s natural immune response. They’re not effective in people with severe Covid-19 who are already hospitalized, but they’ve been shown to prevent hospitalization among those with mild to moderate symptoms. They also seem to protect against infection in high-risk people, acting like a temporary vaccine. Antibody drugs from Eli Lilly and Regeneron have received emergency use authorization from the U.S. Food and Drug Administration.
But one of the authorized antibody drugs, Eli Lilly’s bamlanivimab, was found to be ineffective in treating patients infected with B.1.351, the more transmissible variant first identified in South Africa, according to a study posted January 28 on the preprint server bioRxiv. In another preprint published February 19, a cocktail of two monoclonal antibodies from Regeneron was less effective B.1.351 in lab tests. The drugs still appear effective against the B.1.1.7 variant first reported in the United Kingdom. The two studies have not yet been peer-reviewed.
The problem is that these antibody drugs are based on the original version of SARS-CoV-2 that was initially detected in Wuhan, China. Of course, new variants of the virus are spreading around the world and will likely become even more prevalent. New variants that have mutated spike proteins — the protein the virus uses to get inside human cells — may be able to evade current monoclonal antibodies.
Drug companies are now scrambling to update their antibody drugs to help beat back the variants. In an unusual move, competitors Eli Lilly and GlaxoSmithKline have teamed up to study their antibody drugs together against emerging strains of the virus.
Meanwhile, Massachusetts-based Adagio Therapeutics thinks it has the answer to Covid-19 variants. The biotech company has been looking for antibodies that are effective against existing SARS-CoV-2 strains as well as new SARS-like coronaviruses that might emerge in the future.
“Having another neutralizing antibody against SARS-CoV-2 may be fine, but that’s going to be a short-lived victory because we know these viruses change and mutate,” Adagio CEO Tillman Gerngross, PhD, tells the Coronavirus Blog.
The company has developed antibody drugs that not only neutralize SARS-CoV-2 but also the original SARS virus and additional circulating bat coronaviruses that scientists are actively monitoring. “Our goal is to have the most comprehensive solution to the problem, and that comprehensive solution involves antibodies that are broadly neutralizing across the entire family,” Gerngross says.
“It’s an insurance policy in the event of a future outbreak.”
In February, the company launched an early-stage clinical trial to test its antibody drug in healthy participants. Once it’s shown to be safe, the company plans to take the drug into larger trials for the treatment and prevention of Covid-19, including in countries with high rates of resistant variants.
Hundreds of coronaviruses have been found in animals, particularly bats — the most likely source of the current pandemic. Gerngross and many others believe it’s only a matter of time before another coronavirus spills over into humans. He wants to have a drug ready to go — just in case.
“It’s an insurance policy in the event of a future outbreak,” he says.
The logistics of getting antibody drugs to people who could benefit remains a challenge. They must be given early before patients are sick enough to be hospitalized, so the timing of administering the drugs is tricky. The drugs come in liquid form and must be infused intravenously, meaning patients have to go to a medical center to get treated. The infusion takes around two hours. As a result, antibody drugs are going unused in many states because of a lack of space or staff. In other cases, patients and doctors might not be aware that these drugs are an option.
If antibody drugs are going to be part of the arsenal against new coronavirus strains — and future pandemics — the U.S. health care system will need to figure out how to deploy these drugs quickly and efficiently.