An antiviral drug that was granted an emergency use authorization by the U.S. Food and Drug Administration in December 2021 may be linked to mutations in the virus, according to a new study released on Monday.
Molnupiravir, an antiviral developed by Merck & Co.
works by causing mutations in the virus with the aim of weakening and then killing it, thus reducing the amount of virus in the body.
But the study, which was conducted by a team of mostly U.K.-based academics, found that in some patients, molnupiravir did not succeed in killing the virus but instead allowed the mutated virus to spread.
“Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug,” the authors wrote in the study, which was published Monday in the journal Nature.
Molnupiravir, which is credited with helping vulnerable patients avoid developing severe COVID, was widely used in many countries.
The researchers used a global database to track virus mutations and found changes that looked different from the more typical COVID mutations. The unusual pattern was found to be closely linked to patients who had taken molnupiravir, which is taken orally over five days, and to have increased in 2022, just as molnupiravir was being adopted.
“Our findings show that molnupiravir creates genetically divergent viruses capable not only of replicating but transmitting, with unknown consequences for the global public,” said Ryan Hisner, a researcher at the University of Cape Town in South Africa.
The study did not find that molnupiravir accelerated the creation of new variants of concern, or those that the World Health Organization is tracking more closely.
But the findings should be considered when evaluating the benefits and risks of any of the medications used to treat COVID, the authors wrote.
Merck was critical of the study and said the authors “assume these mutations were associated with viral spread from molnupiravir-treated patients without documented evidence of that transmission.
“Instead, 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.”
The sequences were uncommon and associated with only sporadic cases, it added.
“As noted by the authors, there are limitations to the analyses conducted in this study, which are described in more detail in the manuscript. These data must be considered in the context of all available clinical and non-clinical molnupiravir data,” said Merck.
The study was conducted by researchers at the Francis Crick Institute, the University of Cambridge, Imperial College London, the University of Liverpool, the University of Cape Town and the U.K. Health Security Agency.
The mutations were mostly found in older people, who are more likely to take antivirals, because they are more at risk of developing severe forms of the virus. The mutations were also more prevalent in samples stemming from countries where the drug was more widely prescribed, namely the U.S., U.K., Australia and Japan.
Sales of molnupiravir, which is marketed under the name Lagevrio, came to $5.7 billion in 2022, up from $952 million in 2021.
Merck’s stock was down 0.7% Monday and has fallen 5% in the year to date, while the S&P 500
has gained 13%.