Merck covid drug linked to new virus mutations, study says

Some researchers fear the drug could create a more contagious or health-threatening variation of Covid, which has killed more than 6.8 million people worldwide in the past three years.

Mutations associated with the use of Merck’s Lagebrio tablet have been identified in viral samples from dozens of patients. we at the Francis Crick Institute at Imperial College London and other British institutions.

Drug-related mutations in the virus have yet to be shown to be more immune-evasive or lethal, according to a non-peer-reviewed study published Friday on the medRxiv website. As such, it highlights what some scientists say is a potential risk in the widespread use of the drug. This was recently cleared in China.

LaGevrio works by creating mutations in the Covid genome that prevent the virus from replicating inside the body, making it less likely to cause serious illness. I warned earlier that because of how the drug works, it can cause potentially problematic mutations. The preprint paper reaffirmed concerns about Merck’s drug.

“There was always a fundamental concern that it could contribute to the problem of creating new variants,” said Jonathan Lee, a virologist at Harvard Medical School and Brigham and Women’s Hospital. increase. boston“While this is mostly hypothetical, this preprint validates many of those concerns.”

Merck’s response

Merck disputes the notion that the drug causes problematic mutations.

“There is no evidence that antivirals contributed to the emergence of circulating variants,” Merck spokesman Robert Josephson said by email in response to questions about the study. ) may contribute to the development of new meaningful coronavirus Subspecies. ”

He said new mutations emerged over the course of the pandemic as the virus spread out of control, and LaGevrio could form a key part of the solution. He pointed to a study done in animals that showed that

The study authors speculate that the mutation is related to molnupiravir treatment, but there is no direct evidence that the mutation occurred in patients. Who In a follow-up email, Josephson said they had taken their medication. The conclusion was drawn from the relevance according to the situation.

Merck fell 1.2% new york On Wednesday, it recovered some losses and closed down 0.4%.

The U.S. Food and Drug Administration, which approved Lagevrio in late 2021, would not comment on the third-party study, saying it would work with Covid drug companies to evaluate the product’s activity against subspecies.

preprint

Major scientific journals do not publish research until after the “peer review” process, in which the research is scrutinized by outside experts, is completed. During the pandemic, scientists began to publish their research on what are known as “preprint servers” prior to in-depth research. Reviews, attempts to advance science faster and share urgent discoveries.

Researchers found mutations induced by Lagebrio in a small cluster of patients. This indicates that new versions are spreading among them. According to Ryan Hissner, an independent Indiana researcher who helped write the paper, the largest group they found with similar mutations was 21, but virus samples from many patients had been analyzed. , and may not fully represent the true scope of the problem. .

Researchers examined approximately 13 million viral genomes in databases worldwide.Drug-associated mutations are more likely to occur in countries and groups where Lagebrio is likely to be used, particularly in the United States and Australia, where it was introduced earlier. Signature mutations are less frequent in Canada. Franceand other countries where the drug is not used.

“These effects can be seen in these databases,” said Theo Sanderson, a geneticist at the Crick Institute who led the study.

Hisner said the risk of drug-related mutations was too great to continue using Merck’s drugs. US should consider approving drugs used in other countries to control Covid, like Japan-based Shionogi’s Xocova, and stop using Lagevrio, Stanford says said Michael Lin, an antiviral drug researcher at the university. Not involved in research. China Having cleared La Ghebrio late last year, Shionogi said it was in the final stages of discussions with national regulators on Covid drugs.

“This is a very dire situation,” said Lin. bad things will happen. ”

Sanderson declined to comment on whether doctors should continue to use Merck’s drug, saying the study did not address the issue.

lingering concern

Concerns about the safety and efficacy of Lagevrio have persisted for many years. Health authorities do not recommend use by pregnant women. In general, according to the US National Institutes of Health, this drug should not be used when alternatives are available.

Merck was encouraged by former Warp Speed ​​scientist Moncef Slaoui to work with Ridgeback Biotherapeutics LP to make the much-needed oral Covid pills widely available. Early results showed that the risk of hospitalization and death in unvaccinated people was reduced by about 50%.

Subsequent studies have shown that it is actually less effective than early trials showed. There was no reduction in deaths and deaths, but the time to recovery from symptoms was shortened by several days.

However, Covid treatment options are dwindling. Mutants mutated to evade Covid antibodies created by Regeneron Pharmaceuticals Inc., Eli Lilly & Co., and Vir Biotechnology Inc. The last remaining active, AstraZeneca Plc’s Evusheld, has just been removed from the US market. That means Paxlovid and Gilead Sciences’ remdesivir alone should be injected three times a day as soon as someone is diagnosed.

Paxlobid contains an ingredient called ritonavir, which makes some patients ineligible to take paxlobid.

Raymond Skinazi, a researcher at Emory University, expressed concerns about Merck’s drug early in its development. He had done his own research many years before abandoning it.

After learning about the new research, he called for more surveillance to investigate whether viruses with drug-related mutations had any effect.

Preprint studies are “still an orange flag, not a red flag,” Schinazi said. “Please proceed with caution.”