Merck's Covid medicine linked to virus mutation patterns, says study

By John Lauerman

Merck & Co.’s antiviral Lagevrio is linked to specific genetic changes in the virus that causes Covid-19, researchers said, raising questions about whether the drug has the potential to accelerate how quickly the coronavirus mutates. 
 

Viral samples from patients who took the drug show a “signature mutation profile,” meaning changes were triggered by the drug, the authors said Monday in the journal Nature. The findings adds weight to earlier work by the same team of researchers that suggested that drug-induced mutations of Covid were spreading in some populations, although not in great numbers. 

“We can’t say that this drug makes it more or less likely that a concerning variant will evolve — that’s a question we can’t answer,” Theo Sanderson, the lead author of the study and a researcher at the Francis Crick Institute in London, said in an interview. The researchers said more studies are needed. “Regulators will have to weigh up the benefits of using the drug along with the potential risks.”

When the researchers first published findings about mutations from Merck’s drug in February, the company disputed the idea that Lagevrio was causing problematic new variants. Based on data at the time, the drugmaker said it didn’t believe its treatment was likely to contribute to mutations. 

Lagevrio, also known as molnupiravir, works by creating mutations in the Covid genome to prevent the virus from replicating, reducing its ability to cause severe illness. The emergence of the treatment-associated mutation pattern suggests that some versions of the virus continue to survive and spread even after exposure to the drug, the authors said. They cautioned that the drug-induced mutations they found have yet to lead to a widely circulating new strain of Covid.

Merck’s drug has long been controversial because it can create genetic mutations. Pregnant women are discouraged from taking it, and the Food and Drug Administration recommends against using Lagevrio during pregnancy or breastfeeding. The drug isn’t authorized in patients under 18 because it may affect bone and cartilage growth. 

It’s often given to people who can’t take Pfizer Inc.’s Paxlovid, which interacts with other common medications. So far, Paxlovid has far outperformed Lagrevio. Paxlovid sales were almost $19 billion in 2022, while Lagevrio’s were about $5.7 billion.

In the most recent study, researchers from the US and UK sifted through databases containing some 15 million Covid genomes globally. After Lagevrio hit the market in 2022, they saw the rise of a mutation pattern that appeared to be linked to the drug. Earlier studies by the same researchers showed the pattern was localized to countries using Lagevrio.

“The observation that molnupiravir treatment has left a visible trace in global sequencing databases,” the researchers said in the study, “will be an important consideration for assessing the effects and evolutionary safety of this drug.”