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Antiviral pills work well against Omicron, antibody drugs are less effective: lab study

A new study suggests that current antiviral pills being used to treat COVID-19 remain effective against the highly transmissible Omicron variant, while intravenous antibody drugs appear to be "substantially" less successful.

Researchers at the University of Wisconsin-Madison report that the drugs behind the new oral pills have proved successful in lab tests, and say it would be "welcome news" if the anti-viral pills are confirmed to work against Omicron in human patients.

However, lab tests also revealed that the currently available antibody therapies, which are typically given intravenously in hospitals, are less effective against Omicron than earlier variants of the virus.

The researchers say some antibodies showed to have "entirely lost their ability to neutralize Omicron at realistic dosages."

The findings, published Wednesday in the New England Journal of Medicine, are in line with other studies that show most available antibody treatments are less effective against Omicron, according to researchers.

"The bottom line is we have countermeasures to treat Omicron. That's good news," said lead author and virologist Yoshihiro Kawaoka in a press release. "However, this is all in laboratory studies. Whether this translates into humans, we don't know yet."

Data has shown that various antiviral pills, including from Pfizer and Merck, can help reduce the severity of COVID-19 in at-risk patients if taken early in the course of infection. Experts say approval of such medication could help decrease the burden of the pandemic on hospitals.

Researchers note that COVID-19 antiviral pills were designed and tested before the Omicron variant was identified. Data has shown the Omicron variant is more heavily mutated than earlier versions of the virus, meaning it can spread more readily and even evade antibodies from prior infection or vaccination.

However, the findings suggest that mutational differences do not reduce the effectiveness of drugs designed to treat the original virus strain.

DIFFERENCE IN TREATMENTS

In lab experiments using non-human primate cells, researchers tested multiple antibody and antiviral therapies against the original strain of COVID-19, as well as some of its prominent variants, including Alpha, Delta and Omicron.

According to the study, Merck's antiviral pill molnupiravir and the intravenous drug remdesivir were just as successful against the Omicron variant as they were against earlier virus strains.

Instead of testing Pfizer's oral Paxlovid pill, the study's authors analyzed a related drug by Pfizer that is given intravenously and currently in clinical trials. Researchers found that both drugs disrupted the same part of the "viral machinery," retaining their effectiveness against Omicron.

However, researchers say the tested antibody treatments were overall less effective against Omicron than antiviral pills.

Two antibody treatments -- sotrovimab by GlaxoSmithKline and Evusheld by AstraZeneca -- retained some ability to neutralize the virus, but required anywhere from three to 100 times more of the drugs to do so, according to the study.

The study found antibody treatments by Lilly and Regeneron were also unable to neutralize Omicron at their regular dosages.

Researchers say these results are expected given the different mutations in the Omicron variant's spike protein.

The study notes that most antibody treatments were designed to bind to and neutralize the original spike protein, and any major changes to the protein can make the antibodies less likely to attach.

In comparison, antiviral pills for COVID-19 target the "molecular machinery" the virus uses to make copies of itself once inside cells. Data shows the Omicron variant only has a few mutations to this machinery, which makes it more likely that these drugs will retain their ability to disrupt the replication process, researchers say.

While the effectiveness of the antiviral pills against Omicron is "welcome news," researchers say global health agencies cannot currently use the medication as a common treatment for COVID-19 due to limited supply.

The study's authors say they are now focused on testing new antibody candidates in an attempt to identify those that could potentially neutralize the Omicron variant.

Public health officials around the world have been working to approve anti-COVID pills, with Health Canada authorizing the use of Pfizer's antiviral treatment earlier this month.

The federal health agency says Paxlovid is the first oral and at-home prescription medication to be cleared for use in Canada, and can be given to adults ages 18 and older to treat mild to moderate cases of COVID-19, if they have a confirmed positive test and are at a high risk of becoming seriously ill.

Health Canada has also been reviewing Merck's molnupiravir pill since mid August.

In late December, the U.S. Food and Drug Administration issued an emergency use authorization for both Pfizer and Merck’s drugs.

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