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Why COVID pills are likely to maintain efficacy against the Omicron COVID variant—even if vaccines don’t

December 1, 2021, 11:07 AM UTC

Drugmakers say they are confident emerging antiviral drugs will prove effective in combating the Omicron variant even as they acknowledge that existing vaccines provide less protection against the new strain.

Pfizer CEO Albert Bourla told CNBC this week that he has a “very high level of confidence” that Pfizer’s antiviral pill “will not be affected by this [Omicron] virus.” Pfizer’s pill, called Paxlovid, reduced deaths and hospitalization by 89% among COVID-19 patients in clinical trials, but the U.S. Food and Drug Administration is still reviewing Pfizer’s application to authorize the drug for emergency use.

Pharmaceutical giant Merck, which developed an antiviral pill called molnupiravir in partnership with U.S. based biotech firm Ridgeback Biotherapeutics, also said Tuesday that it expects its drug, which reduced the risk of deaths and hospitalizations by 30% against other COVID-19 variants, to perform similarly against Omicron. This week, a Food and Drug Administration panel voted to recommend that the agency approve Merck’s antiviral pill for emergency use, and a final decision on its approval could come later this month.

The WHO labeled Omicron a “variant of concern” on Friday after it was first detected in South Africa, and since then over 20 countries have confirmed Omicron cases while dozens more have imposed travel bans or other curbs to keep or delay the variant from entering their borders owing to concerns that Omicron might be more transmissible and vaccine-resistant than previous variants.

Bourla’s confidence in Pfizer’s antiviral pills contrasted with his doubts about how the company’s COVID-19 vaccine will fare against the new variant.

“I think the result could be, which we don’t know yet, the vaccines protect less [against Omicron than the Delta variant],” he said. Pfizer’s mRNA COVID-19 vaccine, codeveloped with Germany’s BioNTech, is one of the most widely deployed vaccines in the world and has proved highly effective in limiting transmission of Delta and preventing hospitalizations and deaths from the globally dominant strain. Moderna CEO Stéphane Bancel also said Tuesday he expects a “material drop” in the effectiveness of Moderna’s mRNA COVID-19 vaccine against Omicron compared with Delta.

Dr. Siddharth Sridhar, a clinical virologist at Hong Kong University’s medical school, said the difference between how Pfizer’s antiviral pill and its vaccine will perform against Omicron comes down to the new variant’s unique mutations.

Most of Omicron’s mutations are concentrated on the spike protein, the part of the virus that binds cells to our bodies, he said. “The spike protein has been a big target all along for vaccine manufacturers because, theoretically, if you can get antibodies [to protect] against the spike protein, that protects you from infection,” he said. Sridhar said he expects existing vaccines to still provide a “decent” level of protection against severe disease and death from Omicron, but the “number and type of mutations” in the variant suggest that the vaccines may lose some potency.

But the process through which antiviral pills elicit an immune response is “completely independent of what goes on in the spike,” he noted. Instead, antiviral pills from Merck and Pfizer target proteins that have relatively fewer mutations in Omicron, making it more likely that the antiviral pills will remain effective against the variant.

Bourla said Pfizer designed the antiviral pill to avoid the spike protein, in part, because it is susceptible to mutations.

“The good news is when it comes to our treatment, it was designed with that in mind; it was designed with the fact that most mutations are coming in the spikes,” Bourla said. Mikael Dolsten, Pfizer’s chief scientific officer, echoed Bourla’s remarks in an interview with NPR. “We feel very confident that our new oral Paxlovid drug is going to be highly active against Omicron,” Dolsten said.

But experts caution that it may be days or weeks before there is data to confirm how pills or vaccines behave against Omicron. Ben Cowling, chair of epidemiology at Hong Kong University, said it will be more difficult to collect hard data on how well antiviral pills will perform against Omicron compared with vaccines.

“[For vaccines], it’s quite straightforward to have an approximation of how well they’ll protect against different variants because we have the blood samples. We can go back and test [blood samples] for antibodies to the Omicron variant,” Cowling recently told Fortune. “For antiviral drugs, there’s no compatible test. We really have to test it in the field [to see if the antiviral pills work against Omicron].”

But the same spike protein mutations that may reduce the effectiveness of vaccines against Omicron may also limit the effectiveness of other treatment options.

On Tuesday, U.S. pharmaceutical firm Regeneron, which produces a monoclonal antibody product that has become a commonly used treatment option for high-risk patients, announced that its drug may be less potent in treating Omicron infections compared with previous variants. Researchers also said there are early signs that pharmaceutical giant Eli Lilly’s monoclonal antibody drug may lose efficacy against Omicron. “We would expect [Eli Lilly’s and Regeneron’s antibody drugs] to be very significantly affected by Omicron” because they target the spike protein, noted Sridhar.

Eli Lilly told the Wall Street Journal that it’s too early to speculate about its drug’s effectiveness against Omicron. In a statement to Fortune, Regeneron said there has been no direct data testing “Omicron variant’s resistance to vaccine-induced and monoclonal antibody-conveyed immunity” but that structural modelling and analysis indicates some “reduced reduced neutralization activity” that would limit the effectiveness of its treatment drug. Eli Lilly did not immediately respond to Fortune’s request for comment.

Ultimately, how vaccines, antiviral pills, or other treatments respond to Omicron will only matter on a large scale if the variant spreads widely. For now, scientists are uncertain if it will become globally dominant like Delta or remain marginal like previous Gamma or Beta variants.

“There are many determinants of how likely a virus is going to go global that we actually don’t understand very well yet. And we have to acknowledge that it’s very early days for Omicron,” said Sridhar. “Is Omicron going to replace Delta? It’s a golden question…But what happens next to a certain extent is anyone’s guess.”

This article has been updated to reflect a statement from Regeneron and to note that Merck developed its antiviral pill in partnership with Ridgeback Biotherapeutics.

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