As coronavirus concerns increase with the changing of the seasons, the most commonly used oral antiviral treatments are in the spotlight once again.
Last week, a real-world study of Pfizer’s Paxlovid showed that it has become less effective in keeping at-risk patients out of the hospital as the virus has evolved. And, now, experts have linked Merck’s Lagevrio (molnupiravir) to an increase in mutations, suggesting that its use may have hastened the evolution of new variants.
Lagevrio acts by introducing mutations, destroying the virus's ability to replicate. But if patients treated with the antiviral do not fully clear their infections, “there could be the potential for onward transmission of molnupiravir-mutated viruses,” said the report, which was conducted in the U.K. by researchers from the Francis Crick Institute, the UK Health Security Agency, Imperial College London and the universities of Cambridge, Liverpool and Cape Town.
The report, which was published in Nature, was based on examination of 15 million COVID genomes. It showed that the number of mutations increased after molnupiravir was introduced in several countries.
Merck, which developed the drug along with Ridgeback Biotherapeutics, disputes the report, saying clinical data show molnupiravir “impairs viral replication and reduces viral shedding which would reduce the risk of transmission.”
Merck also pointed out that the researchers assumed mutations were associated with viral spread from molnupiravir-treated patients without documented evidence of that transmission.
“The authors rely on circumstantial associations between the region from which the sequence was identified and timeframe of sequence collection in countries where molnupiravir is available to draw their conclusions,” Merck added.
The drug was approved by the FDA in December 2021 for recently infected patients who are at risk of progressing to a severe form of the virus. It was rejected by regulators in Europe, however, because its clinical benefit could not be demonstrated.
While the authors pointed to the potential for increased transmission of mutated viruses, they added that there is no evidence use of Lagevrio has produced more transmissible or severe COVID variants.
Lagevrio registered sales of $5.7 billion in 2022 despite clinical trials showing Paxlovid had superior efficacy—89% versus 30%—in reducing the risk of hospitalization and death.
In 2023 and as COVID infections have dropped, sales of Lagevrio have dissipated. The company expects revenue from Lagevrio to reach $1 billion this year.
Last week, data from the Cleveland Clinic showed that Pfizer’s Paxlovid was only 37% effective in keeping patients out of the hospital but had retained its ability to help keep patients alive, with efficacy still at 84%.