Research Finds Current COVID-19 Pills Effective Against Omicron, Antibody Drugs Less So

Although current anti-COVID-19 pills are very effective against the omicron variant, lab tests have found that the available antibody therapies are substantially less effective. Some antibodies have entirely lost the ability to neutralize the omicron variant at realistic dosages, according to a study by researchers at the University of Wisconsin-Madison.

Because the research involved laboratory tests, the study authors noted that the efficacy of the antiviral pills needs to be confirmed in human patients. Public health officials expect the pills to become a common treatment for patients with COVID-19 to reduce the severity of the disease in at-risk patients and decrease the burden of the pandemic. The pills are currently in short supply during the omicron wave, according to the study authors.

The study findings corroborate other research showing that most available antibody treatments are less effective against the omicron variant. Drug manufacturers could develop new antibody drugs targeted at the variant to overcome the limitations of current therapies, but this process would take months.

“The bottom line is we have countermeasures to treat omicron. That’s good news,” said study lead Yoshihiro Kawaoka, PhD, in the press release. “However, this is all in laboratory studies. Whether this translates into humans, we don’t know yet.”

The available pills and antibodies were developed before the emergence of the omicron variant, which has significant differences from earlier COVID-19 variants. When the omicron variant was identified, researchers expressed concerns that the mutations in the viral genome could reduce the efficacy of drugs designed to treat the original form of the virus.

In lab experiments using non-human primate cells, Kawaoka and his colleagues tested a suite of antibody and antiviral therapies against the original strain of the COVID-19 virus and its prominent variants, including the alpha, delta, and omicron strains. According to the study, the pill molnupiravir and the intravenous drug remdesivir were just as effective against the omicron variant as they were against earlier strains.

Instead of testing Pfizer’s nirmatrelvir and ritonavir combination (Paxlovid), the team tested a related drug that is administered intravenously. Both drugs disrupt the same part of the viral machinery, and the researchers found that the intravenous drug retained its efficacy against the omicron variant. This version of the drug is currently in clinical trials, according to the press release.

Unlike the antiviral pills, all 4 antibody treatments tested in the study were less effective against omicron than against earlier variants. Two treatments—sotrovimab and a combination of tixagevimab and cilgavimab—retained some ability to neutralize the omicron variant. However, they required anywhere from 3 to 100 times more of the drugs to neutralize the omicron variant. Furthermore, antibody treatments from Lilly and Regeneron were unable to neutralize the omicron variant at common dosages.

These findings were expected, given how the omicron variant differs from earlier strains of SARS-CoV-2, according to the study authors. The omicron variant has dozens of mutations in the spike protein, which the virus uses to enter and infect cells. Most antibodies were designed to bind to and neutralize the original spike protein, so major changes to the protein can make it more difficult for antibodies to attach.

The antiviral pills, however, target the molecular machinery that the virus uses to make copies of itself inside cells. The omicron variant only has a few changes to this machinery, which makes it more likely that the drugs will retain their efficacy, according to the study.

REFERENCE

Current anti-COVID pills work well against omicron, but antibody drugs are less effective. News release. University of Wisconsin-Madison; January 26, 2022. Accessed January 27, 2022. https://news.wisc.edu/current-anti-covid-pills-work-well-against-omicron-but-antibody-drugs-are-less-effective/