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Merck’s oral antiviral pill for COVID-19, molnupiravir — marketed under the name Lagevrio — may be fueling the development of new and potentially deadly variants of COVID-19, according to the authors of a new preprint study.
The study, released Jan. 27 by a team of U.S. and U.K researchers, found, “It is possible that some patients treated with molnupiravir might not fully clear SARS-CoV-2 infections, with the potential for onward transmission of molnupiravir-mutated viruses.”
Merck received significant taxpayer funding from the Biden administration to develop and distribute molnupiravir, and the U.S. government bought nearly 2 million courses of the drug on the taxpayer’s dime.
The study, which is pending peer review, followed the discovery by a middle school science and math teacher in Indiana who found numerous variants of COVID-19 emerged after molnupiravir began to be widely distributed.
Scientists had long warned that the development of such mutations from the use of molnupiravir was possible.
“It’s not a surprise that molnupiravir could cause [the] escape of mutant virus strains or substrains into the population,” said Dr. Harvey Risch. “Its main function is to get the virus to mutate faster.”
Risch, professor emeritus and senior research scientist in epidemiology (chronic diseases) at the Yale School of Public Health, told The Defender:
“The idea is that it will mutate itself to death. But some live mutants could get out, and this paper gives evidence that they have.”
Brian Hooker, Ph.D., P.E., chief scientific officer for Children’s Health Defense, said the study’s authors scanned global SARS-CoV-2 sequence databases looking for mutations characteristic of those by molnupiravir (G-to-A and C-to-U) and found an uptick of those mutants starting in 2022 — after molnupiravir was put on the market and specifically in countries where molnupiravir was distributed.
“Although this isn’t ‘direct proof’ that the mutations came directly from molnupiravir use,” Hooker told The Defender, “the evidence is very compelling, confirming the fears of many who warned of this prior to FDA [U.S. Food and Drug Administration] approval of the drug in late 2021.”
The FDA granted molnupiravir Emergency Use Authorization (EUA) on Dec. 23, 2021, for use in mild-to-moderate COVID-19 infections in patients 18 and over.
The EUA came just one day after the FDA authorized Pfizer’s COVID-19 antiviral treatment Paxlovid.
Merck this week announced massive revenues from sales of molnupiravir in 2022, but projected a significant decrease in those sales in 2023.
The FDA on Wednesday removed the requirement that a person has to test positive for COVID-19 in order to get a prescription for molnupiravir or Paxlovid.
‘I think we are courting disaster’
Molnupiravir “works by creating mutations in the COVID-19 genome that prevent the virus from replicating in the body, reducing the chances it will cause severe illness,” according to Bloomberg.
However, according to Science, the findings of the preprint study suggest “some people treated with the drug generate novel viruses that not only remain viable, but spread.”
This finding “underscores the risk of trying to intentionally alter the pathogen’s genetic code,” leading some researchers to “worry the drug may create more contagious or health-threatening variations of COVID,” Bloomberg reported.
Virologist William Haseltine, Ph.D., chair and president of ACCESS Health International, has repeatedly raised such concerns about molnupiravir.
“It’s very clear that viable mutant viruses can survive [molnupiravir treatment] and compete [with existing variants],” Haseltine told Science. “I think we are courting disaster.”
According to the Gateway Pundit, “When one studies how Lagevrio works, this should not come as a shock. The pill attacks the COVID virus by trying to alter its genetic code.”
The Gateway Pundit reported:
“Once inside a human cell, a virus can make 10,000 copies of its genetic code in a few hours. Each copy made increases the risk the virus makes a rare mistake and creates an inexact replica.
“This is how mutations happen as we have seen with COVID. A drug that deliberately alters a virus’s genetic code would greatly increase the mutation risk.”
Dr. Jonathan Li, a virologist and the director of Li Laboratory, associated with Harvard Medical School and Brigham and Women’s Hospital, told Bloomberg:
“There’s always been this underlying concern that it could contribute to a problem generating new variants. This has largely been hypothetical, but this preprint validates a lot of those concerns.”
According to Science, Haseltine and other scientists have long worried that molnupiravir would create COVID-19 mutations that “would survive and propagate — and perhaps turn out to be more transmissible or virulent than before.”
A Merck spokesperson described that theory as “an interesting hypothetical concern,” prior to the drug receiving EUA.
The same scientists also worried that aside from the virus, the DNA of those receiving the drug might also mutate, Science reported.
These concerns led “researchers and citizen scientists” to examine COVID-19 genome sequences cataloged in the international GISAID (Global Initiative on Sharing Avian Influenza Data) database, seeking to identify mutations likely to be caused by molnupiravir.
‘Clearly something is happening here’
Searching for these mutations was based on the premise that, “Rather than inducing random changes in the virus’ RNA genome, [molnupiravir] is more likely to cause specific nucleic acid substitutions, with guanine switching to adenine and cytosine to uracil,” added Science.
Through this process, Ryan Hisner, a middle school science and math teacher from Monroe, Indiana — described by Science as a “virus hunter” — ultimately “identified dozens of sequences that showed clusters of those hallmark substitutions.”
Hisner took to Twitter with his concerns, where he came into contact with Thomas Peacock, Ph.D., a virologist at the Imperial College London. They and other U.K. and U.S. researchers “systematically reviewed more than 13 million SARS-CoV-2 sequences in GISAID and analyzed those with clusters of more than 20 mutations,” according to Science.
The team found “a large subset showed the hallmark substitutions; all dated from 2022, after molnupiravir began to be widely used,” Science reported.
According to the preprint study, Molnupiravir, “acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal.”
However, the researchers wrote:
“It is possible that some patients treated with molnupiravir might not fully clear SARS-CoV-2 infections, with the potential for onward transmission of molnupiravir-mutated viruses.
“We set out to systematically investigate global sequencing databases for a signature of molnupiravir mutagenesis. We find that a specific class of long phylogenetic branches 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.
“Our data suggest a signature of molnupiravir mutagenesis can be seen in global sequencing databases, in some cases with onwards transmission.”
Peacock told Science these “signature clusters” were up to 100 times more likely to be identified in countries where molnupiravir was widely used, including the U.S., U.K. and Australia, as compared to countries such as Canada and France, where it was not in widespread use.
“Clearly something is happening here,” said Peacock.
Merck: ‘no evidence’ any antiviral agent has contributed to the emergence of circulating variants’
Theo Sanderson, Ph.D., a geneticist at the Francis Crick Institute and co-author of the preprint, told Science “We are not coming to a conclusion about risk” just yet, with regard to whether or not these mutations may lead to more severe COVID-19 variants.
Indeed, according to the preprint study, the variants identified by the researchers have not been shown to be more lethal or more evasive to immunity than other existing strains of COVID-19.
However, Haseltine illustrated the potential risk via the analogy of owning a pet lion: “Just because it didn’t bite you yesterday doesn’t mean it won’t bite you today.”
According to the Gateway Pundit:
“Merck was warned by multiple scientists their drug might create problematic mutations which would render the virus more dangerous and difficult to treat. The company decided to blow off any concerns and put Lagevrio [molnupiravir] on the market anyway.”
As previously reported by The Defender, Dr. James Hildreth, president and CEO of Meharry Medical College and member of Biden’s COVID-19 Health Equity Task Force, expressed concerns about mutant variants escaping.
In 2021, Hildreth told an FDA advisory panel, “Even if the probability is very low, one in 10,000 or 100,000, that this drug would induce an escape mutant from which the vaccines we have do not cover, that could be catastrophic for the whole world actually.”
Also in 2021, Haseltine told Science:
“You are putting a drug into circulation that is a potent mutagen at a time when we are deeply concerned about new variants. I can’t imagine doing anything more dangerous.
“If I were trying to create a new and more dangerous virus in humans, I would feed a subclinical dose [of molnupiravir] to people infected.”
Two other recent studies also called out molnupiravir, questioning its effectiveness and raising concerns the drug may help lead to the development of new COVID-19 variants.
A December 2022 preprint by a team of Australian researchers, found “this commonly used antiviral can ‘supercharge’ viral evolution in immunocompromised patients, potentially generating new variants and prolonging the pandemic.”
And a study published Jan. 28 in The Lancet found, “Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community.”
University of Cambridge clinical microbiologist Ravindra Gupta, Ph.D., told Science that while it’s unclear whether molnupiravir will cause deadlier COVID-19 variants, the overall results of these recent studies “call into question whether molnupiravir should be used.”
Merck spokesperson Robert Josephson defended the product, telling Bloomberg, “There is no evidence that any antiviral agent has contributed to the emergence of circulating variants.”
Molnupiravir ‘different’ than Paxlovid — and ‘riskier’
Although molnupiravir is similar to Paxlovid in that both are oral antiviral treatments for COVID-19, Hooker told The Defender there are significant differences in how the two drugs work:
“Molnupiravir acts on the SARS-CoV-2 virus by directly inducing mutations in the RNA genome. This is a completely different mode of action compared to Pfizer’s product, Paxlovid, and in my estimation is quite dangerous.
“Merck claimed the mutation rate induced by molnupiravir would kill the virus and that mutants wouldn’t escape, but that has been shown to be false in studies of immunocompromised patients.”
Hooker said Paxlovid — and the COVID-19 vaccines — can potentially lead to the development of mutations as well.
But in his view, the “mechanism of action” used by molnupiravir is different — and far riskier — than Paxlovid and COVID-19 vaccines, which merely increase the virus’ lifetime in the human body, giving the virus a greater opportunity to naturally mutate.
Hooker said:
“In contrast, molnupiravir directly induces mutations and thereby vastly increases the mutation rate of the virus in the human host.
“In my estimation, this is a very dangerous way to treat such an infection, given the implications of creating random mutants.”
Merck made billions from molnupiravir — thanks to taxpayers
In 2022, sales of Merck’s molnupiravir hit $5.68 billion, fueled in part by strong fourth-quarter sales of the drug in Asia.
Fourth-quarter sales of molnupiravir reached $825 million, more than doubling analyst expectations of $358 million.
These strong earnings were boosted by government — or taxpayer — support.
In June 2021 — with molnupiravir still in clinical trials, which weren’t completed until October 2021 — the federal government signed a $1.2 billion contract with Merck for 1.7 million courses of the drug, at a cost of approximately $712 per patient.
An analysis by Melissa Barber of the Harvard T.H. Chan School of Public Health and Dzintars Gotham of King’s College Hospital in London found the cost of production of molnupiravir was approximately $1.74 per unit — or $17.74 for a five-day regimen.
By those calculations, the U.S. government paid a near-4,000% markup.
In March 2022, during his State of the Union address, President Biden announced the “Test to Treat” initiative, which allowed those who tested positive for COVID-19 at a pharmacy to obtain free antiviral pills — including molnupiravir — on the spot.
One month earlier, the Biden administration had proceeded with a new purchase of 3.1 million courses of molnupiravir, with the option to purchase more.
Estimates for Merck, and other COVID-19 drugmakers, are less rosy for 2023, as the public tires of all things pandemic and Biden looks to end the COVID-19 national emergency in May.
According to Reuters, sales of molnupiravir are expected to fall to about $1 billion this year, contributing to an expected decline in sales for Merck from $59.3 billion in 2022 to $57.2-$58.7 billion this year.
Merck’s stock price dropped by about 2% with Thursday’s announcement.
Despite these large earnings, overall sales of molnupiravir lagged significantly behind Paxlovid in 2022. Sales of Paxlovid reached $18.9 billion last year.
