Giving Emergency Use Authorization (EUA) to Molnupiravir is absolutely the worst decision ever made in the entire history of the FDA.
By approving Molnupiravir,
the FDA has irreparably
destroyed its reputation.
Please take the time to read the articles below.
FDA authorization of Merck COVID pill called "worst decision in its history"
Critics of the authorization of a new pill to treat COVID-19 are concerned over efficacy, side effects and the drug's potential to generate new viral variants.
Just a few months ago molnupiravir, being developed by pharma giant Merck, was being mooted as a game-changing new drug that could turn the tide of the pandemic. It was one of the first antiviral pills to directly target SARS-CoV-2, and a preliminary Phase 3 trial announcement indicated promising efficacy.
But as the weeks passed molnupiravir quickly lost its luster. Pfizer’s novel antiviral pill raced to the head of the pack with impressive clinical trial data, while a final analysis of molnupiravir’s Phase 3 data revealed a stark drop in efficacy, down to levels bordering on insignificant.
While Pfizer’s final trial analysis reported up to 90 percent protection from COVID-19 hospitalization or death, molnupiravir’s efficacy strangely dropped from interim analysis to final reporting. Initially Merck announced molnupiravir delivered around 50 percent protection from COVID-19 hospitalization or death but a final trial analysis weeks later revealed that efficacy had dropped to barely 30 percent.
Alongside the disappointing efficacy data, questions began to arise over the drug’s safety profile, on both individual and societal levels.
Molnupiravir is a very different drug to Pfizer’s COVID antiviral Paxlovid. Pfizer’s drug is specifically targeted at SARS-CoV-2, working to inhibit the activity of a key enzyme the virus needs to replicate. Molnupiravir, on the other hand, targets RNA viruses in general. It was originally developed in 2018 as a tool to treat influenza, and lab work revealed it potentially worked against other RNA viruses including Ebola and the first SARS coronavirus.
It works by generating transcription errors as a virus replicates. This essentially produces a massive volume of downstream mutations in a virus as it replicates and this quickly leads to major dysfunction in the viral copies.
While there were no significant adverse effects reported in molnupiravir’s Phase 3 clinical trial, its particular mode of action has concerned some experts who argue this mutagenic mechanism could theoretically cause problems in some fast-growing human cells. As an FDA advisory panel debated the safety and efficacy of molnupiravir in late November, the main safety issue they raised was whether the drug should be offered to someone who is pregnant.
The independent advisory panel ultimately voted to recommend approval of molnupiravir, but the result was far from unanimous. A divisive 13-10 vote led a Merck representative at the meeting to affirm the company would not recommend pregnant individuals take the drug. However, the representative also indicated these decisions should be made in conversation between patients and their individual doctors.
“We would not recommend its use in pregnancy and we would also recommend contraception in women of childbearing age,” the Merck representative was reported as saying. “But I think the idea here is that ultimately the physician is the best position to determine the relative risk benefit for their patients.”
In the FDA’s statement announcing the emergency use authorization of molnupiravir it accepts the drug may cause fetal harm but stopped short of completely disallowing pregnant individuals from being prescribed the drug.
“Molnupiravir is only authorized to be prescribed to a pregnant individual after the prescribing healthcare provider has determined that the benefits of being treated with molnupiravir would outweigh the risks for that individual patient and after the prescribing health care provider has communicated the known and potential benefits and the potential risks of using molnupiravir during pregnancy to the pregnant individual,” the FDA statement notes.
Besides questions of efficacy or individual safety, some experts have also questioned whether molnupiravir’s mutagenic mode of action could accelerate the chances of new variants emerging. A drug that intentionally forces a virus to mutate could, in theory, generate mutations that don’t kill the virus but help it become more virulent.
The concern is entirely theoretical at this stage, but it is a problem. James Hildreth, a HIV researcher from Meharry Medical College, was one of the most vocal on the FDA’s advisory panel to express this concern. He voted against recommending molnupiravir and indicated Merck has not done enough to clearly quantify this potential risk.
“Even if the probability is very low, 1 in 10,000 or 100 000, that this drug would induce an escape mutant which the vaccines we have do not cover, that would be catastrophic for the whole world,” Hildreth said.
Hildreth more recently said he was baffled at the FDA’s ultimate approval of the drug. On Twitter Hildreth questioned why approval would be granted to a drug with only 30 percent efficacy, known birth defect risks and a potential to drive viral mutation, when there is another COVID-19 pill now available that works better and has none of these risks.
Michael Lin, a neurobiologist from Stanford University, was even more frank in his criticism of the FDA’s molnupiravir authorization, calling it “the worst decision in its history.” Lin argues there has never been a drug like molnupiravir authorized for widespread use and there are more effective safer alternatives already developed.
□Dismayed that FDA has now made the worst decision in its history. We cannot give up on raising awareness of the dangers of molnupiravir, and its poor efficacy. We must limit its use while we work on a worldwide campaign to reverse this.https://t.co/2NuYkOcbTp pic.twitter.com/hJlO0wpo50— Michael Lin, PhD-MD □ (@michaelzlin) December 23, 2021
The FDA indicates it has weighed up the risks versus benefits of molnupiravir and deemed it worthwhile considering the current state of the COVID-19 pandemic. It makes clear this is not a full approval of molnupiravir but rather a finite emergency use authorization with limits on its use to adults over the age of 18 at high risk of severe COVID-19 with no access to alternative treatment.
“Based on the FDA’s review of the totality of the scientific evidence available, the agency has determined that it is reasonable to believe that molnupiravir may be effective for use as treatment of mild-to-moderate COVID-19 in certain adults when alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate,” the FDA’s statement reads. “The agency has also determined that the known and potential benefits of molnupiravir, when used consistent with the terms and conditions of the authorization, outweigh the known and potential risks of the product.”
December 23, 2021
PAXLOVID and Molnupiravir: Avoid
My opinion on these drugs is pretty simple: avoid.
The first three Covid drugs approved under EUA were Remdesivir, Baricitinib, and Tofacitinib. All were EUA approved for inpatient use (in hospital) only, demonstrate dismal effectiveness and are replete with black box warnings and side effects such as organ failure, blood clots, serious infections and malignancy.
PAXLOVID was recently approved by the FDA without any external meetings or disclosure. There was no opportunity for public input. Essentially all done behind closed doors.
Dr. Ryan Cole on the drug’s mechanism of action after infection explains, the Covid virus enters the cell and commandeers the cell forcing it to produce proteins. Protease enzymes must be present for the virus to successfully complete the cycle before taking the cell over. PAXLOVID or any drug classified as a ‘Protease Inhibitor’ will inhibit or decrease the Protease enzyme interfering with the virus. Ivermectin is the most successful and proven protease inhibitor in production. Just as with Paxlovid, ivermectin decreases the protease enzyme but...the benefits of ivermectin in Covid treatment are obvious and not present in paxlovid. Additional actions of ivermectin include anti-coagulant action and anti-inflammatory actions, both observed in Covid infections. Hydroxychloroquine is also a protease inhibitor and also works against COVID.
So why PAXLOVID?
Because it’s from big pharma, is less proven than other drugs in terms of safety, and was approved without input from the external committees and the public. If that doesn’t inspire confidence, then I don’t know what does.
You should ask your doctor to explain to you why the off-the-shelf protease inhibitors don’t work, while this one does. Let me know what he says.
PAXLOVID requires combination with an HIV/AIDS drug, Ritonavir, preventing the breakdown of the PAXLOVID so it may inhibit or decrease the enzyme interrupting the viral life cycle. Dr. Cole reports Ritonavir also has its own black box warning and side effects include life-threatening liver, pancreas and heart issues.
According to Pfizer’s press release, PAXLOVID reduces hospitalization/death by 89%. So in the treatment group we had 5 of 697 hospitalized with no deaths compared to 44/682 hospitalized with 9 subsequent deaths.
How does that compare with the Fareed and Tyson protocol?
Well, Fareed and Tyson had 10 times as many patients taking the drug combo and yet they had fewer hospitalizations (4) and the same number of deaths (0).
So you’re way better off with the Fareed and Tyson protocol.
First, the efficacy when it works is poor, only 50%. There were two groups in the randomized trials and in the second group, the people who got the drug ended up worse. And then there is the problem of causing cancer and prion disease. For more, see the Molnupiravir section of this article and this article.
Bottom lineAvoid these drugs.
Early treatments using repurposed drugs have a track record that is safer and more effective than either of two drugs that the FDA likes.
But thanks to the NIH, you’ll never hear about early treatment protocols unless you live in Florida.
December 5, 2021
Covid Drug Molnupiravir: Toxic Chemotherapy for the Genome?
Or a freefloating bioweapon that could destroy the entire ecosystem?https://wholistic.substack.com/p/covid-drug-molnupiravir-toxic-chemotherapy
It’s easy to laugh at Jones, but some of his predictions seem to come true, spawning the saying “Alex Jones is always right.”
The reality behind Alex’s famous rant is that chemicals have been entering our water supply, including many of the common drugs we take. These chemicals include everything from pesticides to hormones from birth control to chemo drugs.
Could they be turning frogs gay? Perhaps not gay per se, but here’s what pesticides can do to frogs...1
“The results show that pesticides with this mechanism of action can cause permanent damage, such as reduced fertility in frogs exposed at the tadpole stage. This supports previous research showing that endocrine-disrupting substances in the environment may negatively impact amphibians. The substance linuron isn’t approved for use in Sweden, but it’s used in other parts of the EU and in North America,” says Cecilia Berg, ecotoxicologist and project leader.
Pharmaceutical drugs are also in our water supply. Did you want to avoid taking psychotropic drugs like Prozac? Too bad, because you might be consuming it even if you don’t want to, seeing as your neighbor may be peeing it out daily.
From The Effects of Drug Production on the Environment:
The Following Are Some of The Most Common Ways that Drugs Contaminate the Environment:
- During the manufacturing process, drug residue may infiltrate surface waters.
- Drugs are metabolized by humans and then excreted in trace quantities into the sewage system. This pollution inevitably finds its way into the water supply after going through treatment systems.
- Veterinary pharmaceuticals are excreted in soils and surface waters by pasture animals.
- The drugs used in livestock can be distributed using manure as a fertilizer.
- Unused drugs are often dumped into public water supplies through sinks, toilets, and landfills.
- During the manufacturing process, direct pollutants are emitted into the atmosphere.
What Happened to the Green Pharmacy Movement?
The issue of pharmaceutical contamination is a huge problem, and one that the media hasn’t really been paying much attention to since the problem first started getting some traction years ago.
There has been some discussion of a green pharmacy movement to help counter some of the ecological problems of modern medicine. But not enough. The idea of a “green pharmacy” seems to have taken a backseat to the dominating environmental narrative of climate change.
My background actually includes environmentalism, and I used to volunteer for a Los Angeles organization called Heal the Bay to collect water samples in the Malibu hills. The septic tanks of the posh celebrity homes were responsible for atrociously high bacterial counts at Malibu beaches, which often scored worse pollution scores (Fs) than seedy Venice Beach, where I lived at the time.
That was probably my first lesson in green hypocrisy.
I even had an environmental blog briefly, focused in part on technology, but it didn’t gain much readership, so I abandoned it. I was ahead of the curve. I wrote a scathing article in the late 2000s about how “climate change” was a terrible issue to focus on, since it was so divisive and overshadowing much more tangible environment problems such as visible pollution in the water and air, issues that maybe left and right could find some common ground on.
Since then, the divide has gotten even worse, and the only “critical” environmental issue is climate change. Sure, we have a big plastic island floating around the Pacific, and Fukushima is still spilling radiation into the sea. We have aging nuclear infrastructure leaking toxins into the environment...did you know about the Red Hill contamination crisis in Hawaii? I only found out about it by accident.
But who cares about all that? Climate change, climate change, climate change!
I’m in disagreement with the right regarding environmental issues as a whole, as I think our entire ecosystem (not just the climate) is under a tremendous amount of stress due to human activity. That said, I’m in disagreement with the left that “climate change” is the number one problem or the only thing we need to focus on.
Climate change is an easy virtue signal, in addition to being a great way for governments to take more control, without actually solving many of the real environment pollution problems we face.
If you pay attention, you’ll notice that climate change narratives generally center around control, much like the covid pandemic. “Climate change” also offers a potentially lucrative new “stock market” consisting of carbon credits...so climate change is environmentalism co-opted for control and money.
But mitigating the damage that pharmaceutical drugs are causing the environment? It’s not profitable and doesn’t lead to any obvious control systems. No wonder it’s ignored.
That said, don’t make the mistake of trying to argue that climate change isn’t real. It’s the same mistake that the “covid isn’t real” people are making.
You get stuck in that argument and end up making yourself look like a flat earther instead of steering and controlling the narrative.
Denial is a defensive position.
I’m going on offense. You can argue whether climate change is real or not until you are blue in the face, but it won’t change a damn thing. But I’m looking to shift the narrative completely.
Let’s talk about how our public health policies might be making everything worse and potentially not just harming people but also the environment.
It’s rather ironic to me that the left has fully embraced the vaccine narrative, because mass vaccination as a whole creates environmental waste in the form of chemical byproducts during production as well as syringe waste.
Natural immunity is much more environmentally sound, and yet you’ll rarely hear an environmentalist suggesting we encourage natural immunity for those who are at an almost zero risk of severe covid.
We should be pointing that out, and frequently.
Worse, some scientists are trying to figure out how to put vaccines in our food supply, which means the vaccines themselves could enter into the general environment, harming not just people but wildlife. This isn’t a new thing, by the way. They have been testing edible vaccines for over twenty years.
We need to get in front of this, like yesterday.
Molnupiravir: Worse Than You Thought
Enter molnupiravir. This is the “game-changing” covid drug that the media has been swooning over while making ivermectin out to be some sort of poison.
The UK is set to be the first country to use molnupiravir, and will be given to vulnerable and elderly patients starting very soon.
If you thought synthetic hormones in the environment were bad, wait until you hear what molnupiravir does.
I can’t do this subject justice. So I recommend that when you are done reading this, head on over to Unglossed and read the article Doppelgänger by Brian Mowrey.
Here’s my attempt to summarize his main points in plain language:
Molnupiravir can “insinuate into viral mRNA, causing errors in replication and translation” and “insinuate into nuclear RNA.”
Errors in viral replication may mean new variants...but that may be the least of the problems. Mowrey mentions the potential for “misfolded proteins” that could go anywhere in the body. We’re potentially talking prions here.
You know, like mad cow prions.
Autoimmunity is also a concern.
Molnupiravir may also get into cell mitochondria, disrupting cellular metabolism, which could starve cells to death.
The drug could potentially compete with natural chemicals that produce cell membranes and protein structures necessary for human cell metabolism.
Here’s the kicker:
Molnupiravir, which we’ll call “M” for short in terms of its chemical action, could vie with natural cellular processes, and accidentally be replicated into DNA during DNA repair. Mowrey writes: “There, M will presumably be misread by polymerase as T instead of C, resulting in cellular metabolic failure leading to apoptosis, or carcinogenesis - conversion into cancer cells.”
(Apoptosis is a fancy term for “cell death.”)
That’s not all:
As with virally-infected cells in the first example, apoptosis of cells containing M would merely release A/U/T/G/C and M bits into the body, where they might be salvaged or excreted. M, unlike most drugs, is possibly not going to ever be truly “metabolized” out of potential active forms. It will only alternate between 2/3phosphate+1/2OHthing+ forms, bounce from cell to cell, and repeat the same interactions until degraded. The “half-life” for M - when it ceases to be available in actively employable forms - in the real world is probably unknowable.
What he means is that mutated cells, thanks to M, may keep the vicious cycle going indefinitely in your body. But that’s not the worst of it:
Excreted M, for example, could enter the microbiotic genome (bacteria in the gut and elsewhere), potentially producing mutant bacteria. Even upon the death of bacterial cells due to lethal mutations during DNA repair and cellular division, M could still be recycled to other bacteria. These bacteria could, of course, carry M to other organisms, conceivably resulting in “wild-caught M-induced carcinogenesis and infertility” throughout every kingdom of life.
Non-excreted, free-floating cellular M, once reduced to lower levels, could end up incorporated into viable RNA and DNA viruses, and transmitted from the original recipient.
Humans will merely be the vector for some amount of M to “infect” the entire nucleoside-metabolic cycle of the Earth, until finally degraded.
In other words, molnupiravir could turn into a sort of environmental “virus” of its own...let’s call it malware with an M.
That malware would first damage your body, then be excreted into the ecosystem, and from there, self-propagate, causing cancer and infertility not just in humans but in animals and wildlife.
This is really, really bad.
Bees were being threatened with extinction a few years back via Colony Collapse Disorder, which is a euphemistic way of saying “bee genocide” by unknown causes. Pesticides have certainly been looked at as a culprit, but what effects might our free-floating pharmaceuticals also have on bee colonies?
It’s not just bees at risk. In and around Washington, DC and several states this summer, songbirds were dying of a mysterious illness. With neurological symptoms and seizures happening, I’m going to suggest that this might have been due to some type of environmental poison or disease...rather than the climate getting too hot or too cold.
Would we even be able to find out if drug waste is impacting these animals?
Would they tell us?
Was Alex Jones right about the friggin’ frogs?
What Exactly Is Molnupiravir Anyway?
Molnupiravir is a nucleoside analog. According to ScienceDirect, “Nucleoside analogs are a pharmacological class of compounds with cytotoxic, immunosuppressive, and antiviral properties.”
Cytotoxic, meaning they kill cells. Immunosuppressive, meaning they suppress the immune system.
I think calling molnupiravir “malware” is not too far off. I’ll leave the last word on this to Mowrey, who wrote this in a follow up post:
Nucleoside analogs, as I argued in “Doppelgänger,” are not “antivirals.” The mechanism of “viral replication” which they seek to sabotage is intrinsic to cellular metabolism, DNA repair, gene expression, cellular division, and sperm cell longevity. Ribavirin, Molnupiravir, and all other analogs in development, essentially seek to cut off the face to spite the nose. It cannot be done without short and long term harms, and profound risks to fertility. This is not a “therapeutic” platform - it is chemotherapy for the genome. It is an appropriate accident at best, that this particular drug was developed with funding from the US Defense Threat Reduction Agency (Ridgeback and Merck only took over after six years of DTRA-funded research24).
And yet not only are nucleoside analog “antivirals” still being aggressively researched, they reside within a cultural blindspot both within the industry and the public at large - they are lethal bioweapons on the scale of Anthrax, inaccurately imagined as “kind of similar to Tamiflu.”
November 30, 2021
FDA panel narrowly recommends authorization of first antiviral pill to treat Covid-19
The FDA is not obligated to follow the advice of the panels it convenes, but it usually does.
The expert panel voted 13-10 that the pill, called molnupiravir, should be authorized, although members expressed concerns that, if used in pregnancy it could cause birth defects. During the panel, discussions frequently turned to whether or not panelists trusted the effectiveness data on the drug, even when they were discussing other topics.
“I think we need to stop and acknowledge that the whole reason we’re having this discussion is because the efficacy of this product is not overwhelmingly good,” said W. David Hardy of Charles Drew University School of Medicine and Science during a discussion about the drug’s use during pregnancy. “And I think that makes all of us feel a bit uncomfortable about the fact whether this is an advance therapeutically because it’s an oral medication, not an intravenous medication.”
The vote is a blow to Merck, which seemed to emerge on Oct. 1 with a pandemic game-changer: the first antiviral pill to reduce hospitalization and death in Covid-19. However, last Friday, Merck released data from the full population of that study, showing the drug’s benefit was substantially reduced. Concerns have also been raised about whether molnupiravir, which works by inhibiting the ability of the virus to replicate its genetic material, might cause birth defects or even long-term effects from damaging patients’ DNA, potentially causing long-term harms like cancer. Both Merck and FDA scientists said such outcomes were unlikely for a medicine that would only be taken for only five days, although they faced tough questions from panelists about the specific animal studies that indicated the treatment was safe.
“Obviously we are pleased with a positive vote and, you know, there was a lot of robust discussion,” Roy Baynes, Merck’s chief medical officer, told STAT. “I think, at this moment in time, based upon all the data, we do believe that overall benefit risk is positive in high risk patients.”
Since Merck’s initial announcement, Pfizer has released interim data on its own Covid pill, also a five-day treatment, which showed 89% efficacy. Full data from that study have yet to read out. Pfizer executives say the FDA has not told it to expect an outside advisory panel. That drug must be given with another medicine, ritonavir, which interacts with many drugs.
On Tuesday, throughout the hearing of the advisory committee, panelists asked pointed questions of both Merck and the FDA, whose scientists had seemed to back the approval of the medicine in briefing documents released Friday. Among them was how to interpret the change in the results around the drug’s effectiveness. The early results released Oct. 1 showed a 50% reduction in hospitalization, or an absolute decrease of 7%. In the final results, the result shrank to a 30% decrease, or a 3% absolute difference in hospitalization in the full population.
Lindsey Baden of the Brigham and Women’s Hospital, the panel chair, asked early on how this could be. “Help me understand,” he said.
Nicholas Kartsonis, a Merck researcher, explained that the interim analysis was the primary analysis, but also said, at length, that Merck’s scientists had not been able to come up with clear reasons for the result. “I don’t have a satisfying answer to your question but at least that’s the totality of the data we have.”
Panelists also worried about data showing that use of molnupiravir might, in theory, lead to new variants of the SARS-CoV-2 virus through its mechanism, which works by causing viruses to make mistakes in copying their genetic material.
“With all respect, I think it’s incumbent upon you to make some effort to make an estimate of what is the likelihood of escape mutants occurring as a result of your drug,” said James Hildreth, a panelist and the CEO of Meharry Medical College.
However, other panelists, including John Coffin, a Tufts molecular biologist, argued that the overall risk of such mutations due to the drug was small.
But the panel was also concerned about safety, both in pregnant women and in patients in general. Merck had argued that the drug should be available in pregnancy in some cases.
Panelists stopped short of saying that the drug should not ever be given during pregnancy. But they recommended it only be used in rare circumstances, such as when other treatments such as monoclonal antibodies are not available or in the event that a new strain of Covid has become resistant to those treatments and that it should be left up to the patient.
One panelist, Sankar Swaminathan of the University of Utah, even wondered aloud whether the drug could cause birth defects if it affects sperm, and if men should be told not to have children for some time after receiving the drug.
“There are definite concerns about the potential effects of this drug on the embryo and the fetus,” said Janet Cragan, a medical officer at the Centers for Disease Control and Prevention and a panelist. “I don’t think you can ethically say it’s OK to give this drug in pregnancy. [But] I’m not sure you can tell a pregnant women who has Covid-19 that she can’t have the drug if she has decided that’s what she needs.”
After the vote, Baynes, the Merck executive, argued the decision should be left with physicians. “”We would not recommend its use in pregnancy and we would also recommend contraception in women of childbearing age,” Baynes said. “But I think the idea here is that ultimately the physician is the best position to determine the relative risk benefit for their patients.”
In the end, panelists narrowly voted that the benefits of having an oral Covid treatment to keep people out of the hospital outweighed their questions and concerns. But the FDA may write a far narrower authorization for the drug than observers would previously have expected.
“This was clearly a difficult decision,” said Michael Green, an infectious disease expert at the University of Pittsburgh, in explaining his “yes” vote.
November 26, 2021
New data, analyses take some of the shine off Merck’s Covid pill
On Friday, the drug maker released full results from its study of the pill, molnupiravir, showing it reduced the risk of hospitalization by 30%, down from a decrease of 50% seen in an earlier analysis. In the 1,433-patient study, fewer patients died when they received the treatment. There were nine deaths in the placebo group in the final analysis, and one in the molnupiravir group.
The data were released as the FDA published its own analysis of molnupiravir ahead of a meeting of advisers being convened by the agency to vote on whether the medicine’s benefits outweigh its risks.
In that analysis, FDA researchers seemed to favor the authorization of molnupiravir but raised concerns that could mean people who are at lower risk from the disease would not be offered the pill.
The fate of molnupiravir — developed in partnership between Merck and Ridgeback Therapeutics — is important for both society’s battle against Covid-19 and Merck’s financial fortunes. Experts say that an easy-to-give, oral treatment that keeps people who contract the SARS-CoV-2 virus from being hospitalized or dying would go a long way toward helping society return to normal. Existing pills, such as hydroxychloroquine or ivermectin, have failed to deliver convincing results.
Monoclonal antibodies treatments, though very effective, must be given as shots or intravenous infusions.
Pfizer recently released results on its own Covid pill, showing an 89% decrease in hospitalizations in an interim analysis.
As governments buy large amounts of both pills, the financial stakes could be enormous. During its October earnings call, Merck said molnupiravir could generate between $500 million and $1 billion this year and between $5 billion and $7 billion next year, according to a transcript STAT obtained through Senteio, a financial database provider. Geoffrey Porges, a stock analyst at the investment bank SVB Leerink, recently estimated that sales of Pfizer’s antiviral Covid pill could reach $24 billion in 2022.
The FDA’s advisory committee will convene on Tuesday to discuss Merck’s pill. The agency is seeking guidance on a few questions: Should pregnant women ever receive this drug? Could the use of this medicine result in the evolution of new, more worrisome variants of the SARS-CoV-2 virus, which causes Covid-19? And, of course, should the medicine be authorized, and for whom?
In a 68-page document independently analyzing the molnupiravir trial results, FDA experts delve into the data behind each of those questions.
The FDA does not seem concerned about one of the main worries that has been raised about molnupiravir: that it could cause mutations in people, thereby leading to cancer or other long-term health problems. A test done on bacteria, known as an Ames assay, did show a risk of mutation, called mutagenicity, the FDA says. But follow-up tests in a particular type of rat did not show a problem, and it is unlikely, the agency says, that such a problem would occur after just five days of treatment.
“Given the negative in vivo assay results, and considering the 5-day treatment duration with MOV, the Agency pharmacology/toxicology experts have concluded the risk of mutagenicity in the clinic is low,” the FDA reviewers said.
But the FDA did have a concern about whether or not molnupiravir should be given to so-called breakthrough cases, people who have been vaccinated against Covid-19 but still get infected. The agency points to a subgroup of patients in the study who had antibodies to Covid-19 who did not seem to benefit from molnupiravir. That group, though, was far too small to draw conclusions.
The FDA also had concerns about using molnupiravir in pregnant women and children. (Merck and the FDA agree that the drug should not be authorized for people under 18.) In studies in rats of a dose much higher than is given to people, researchers saw reductions in fetal body weight as well as “external, visceral, and skeletal malformations” in surviving fetuses.
The FDA proposes two ways of handling the risk in pregnant women. One approach would simply state that no pregnant women should receive the drug. A second would be to include warnings, but allow physicians to prescribe the medicine if they thought it was warranted. The FDA’s advisory committee will be asked to weigh in on which approach to take. The FDA does propose that women should take a pregnancy test before being prescribed the drug.
Nowhere in its analysis does the FDA seem to contemplate not making molnupiravir available. But adding restrictions will make the drug more difficult to give in practice, and could also make the Pfizer pill a preferred option, if data on that medicine hold up better than the data around molnupiravir have. This is a case where the opinions of the FDA’s expert panelists are likely to hold even more weight than usual.
Merck shares dipped almost 4% in morning trading. Pfizer shares rose more than 5%.
November 15, 2021
Cancer And Birth Defects: Potential Risks Of Molnupiravir?
Scientists continue to share their concerns over the potential mutagenic side effects of the candidate COVID-19 drug molnupiravir, as Merck apply for Emergency Use Authorization for the drug.
As part of the efficacy and safety research on molnupiravir, Merck has set criteria for both male and female participants related to reproduction, fueling questions about the drug’s safety in patients of reproductive age. However, despite the potential risks, Merck has continued to ink deals worldwide.
CONCERNS FOR IMPACT ON NEW LIFE?
Participants in Merck’s molnupiravir trials must agree to stringent criteria related to reproduction both during and up to 4 days after the end of the trial. Males must abstain from heterosexual intercourse or use contraception. Women of childbearing potential (WOCBP) must either use a highly effective contraceptive method or abstain from sexual intercourse, and should have a negative pregnancy test result within 24 hours before taking the first dose. Female participants should not be breastfeeding while taking the drug.
The detailed criteria have resurrected queries over the safety of molnupiravir. As the U.S. Food and Drug Administration (FDA) prepare to consider the application for Emergency Use Authorization (EUA) for molnupiravir at the end of November, TrialSite takes a closer look at the science surrounding this pharmaceutical.
MUTAGENIC BY DESIGN
Molnupiravir disrupts the viral replication by introducing mutations during viral RNA replication. William A. Haseltine, an American scientist, Harvard Medical School professor, and businessman discussed how the drug halts SARS-COV-2 through lethal mutagenesis.
- The drug tricks the virus into replicating.
- When replicating, errors are inserted into the genetic code assuming the nucleotide uracil and cytosine
- Once re-replicated, mutations are developed (changing of nucleotides from U to C and C to U)
- Once more faulty codes are copied, the virus is killed, shortening replication and infection period, and transmission.
However, there are two potential negative consequences of this method of action: one to the virus, and one to the patient.
Firstly, it is imperative that the optimal dose is delivered. Use of a suboptimal dose would increase the mutations occurring during viral replication, without ensuring the virus is killed. The result would not only be ineffective treatment, but the potential to produce new variants of the virus itself. These new variants could potentially be more virulent than the original strain.
The second issue of concern is the potential for host DNA to be subject to the same mutagenesis as the viral DNA.
As reported previously on Trialsite, Dr. Raymond Schinazi, an organic medicinal chemist specializing in antiviral agents, pharmacology, and biotechnology, and his scientist colleagues states that NHC, the initial metabolite of molnupiravir, may result in ‘animal cell culture mutations’. Research into the drug was abandoned in 2003 when they found out about its mutagenic properties.
A study published in August 2021 found that NHC is mutagenic to mammalian cells as well as to the COVID virus. Their research on SARS-CoV-2 showed antiviral and mutagenic effects at concentrations as low as 0.3 μM. Using a cell line that allows detection of mutation in a single gene, the scientists reported that doses of rNHC did not inhibit cell growth, but induced mutagenesis in a dose-dependent fashion.
The paper clarified that the experiment involved exposing the cells to the drug for 32 days. The doses of NHC tested were between 0.3 μM up to 3 μM. While all tests involving NHC had greater levels of mutations than the negative control, the values were not statistically significant when NHC concentrations were below 3 μM. The authors specified that these changes would be limited to dividing cells where synthesis of DNA precursors is ongoing.
Merck scientists responded to the publication stating that because the mutation observations were based on lab cell culture, they were “not relevant to how the drug would affect an entire animal.”
However, the scientific community is not convinced. Dr. Rafael R. Castillo, a member of the Board of Medicine in the Philippines, discussed the ability of mutagenic drugs to cause cancer or congenital defects. He stated that although a five-day course should not cause lasting side effects, it should not be recommended for longer courses. He also suggested that the FDA issue precautions and warnings to patients, especially those of reproductive age.
Scientists also raise concerns that the effects of mutations at the molecular level, including cancer and birth defects, may present later in life, meaning it may be hard to prove the causal link with molnupiravir.
PROFIT OVER SAFETY?
Dr. Haseltine wrote in a Forbes article that two prices are going to be paid: when taking molnupiravir: the cost of the drug and its side effects.
Merck secured funding to conduct research on molnupiravir as a potential drug against the COVID-19 virus. Of course the $356 million was thanks to the taxpayer. Rick Arthur Bright, an immunologist, vaccine researcher, and former director of the Biomedical Advanced Research and Development Authority (BARDA), raised his concerns about funding the research of the drug using taxpayers’ money given its mutagenic property. Mr. Bright states that an unauthorized $20 million fund for molnupiravir was given from BARDA’s money.
Despite the questionable funding and questions raised concerning the side effects of the drug, Merck conducted a Phase 3 trial, finding positive results.
Trialsite reported on Merck’s planned tiered-pricing approach for molnupiravir after closing a deal with the US government. Research on molnupiravir pricing showed a calculated cost of about $18-$20 per course of treatment, while it will be sold for 35 times more at about $700 per course. Merck also applied to the FDA on October 11, 2021 for molnupiravir’s emergency use based on their unfinished trial results.
UP TO OLD TRICKS?
This is not the first time Merck have pushed a drug to the front lines despite evidence for its dangerous side effects. Vioxx (rofecoxib) was a pain relief drug targeting arthritic patients, which was approved by the FDA in May 1999 but had to be withdrawn in 2004 for fatal cardiac side effects.
In light of this history of disinformation strategies, Merck’s apparent confidence in the safety profile of molnupiravir should be scrutinized. The fact that they are loudly discrediting the safety profile of their own ivermectin, has led to speculation that they are clearing the way for their profitable, patented alternative.
On November 4, TrialSite reported on the UK’s decision to authorize molnupiravir. This follows its use in parts of Vietnam, and other deals being struck around the world. TrialSite will be watching the FDA’s evaluation of molnupiravir with interest, and will continue to report on these unfolding events.
November 2, 2021
Harming Those Who Receive It: The Dangers Of Molnupiravir (Part 2)
Molnupiravir is a relatively new drug, initially developed as an antiviral treatment for influenza. Molnupiravir’s metabolite, an active compound called NHC, has been known and studied for decades. The metabolite works by creating havoc with RNA polymerase, the enzyme critical for viral replication. As I described in yesterday’s article, the drug inserts errors into the virus’ genetic code every time it copies itself. Insert enough errors and you essentially kill off the virus, preventing it from replicating any further.
Against other coronaviruses, like MERS-CoV and mouse hepatitis virus (MHV), the drug was found to create up to more than a hundred mutations at every section of the viral genome. Against SARS-CoV-2, molnupiravir’s manufacturers Merck and Ridgeback say that the drug’s antiviral effects are powerfully effective, limiting the virus’ ability to proliferate unchecked and cutting the risk of hospitalization and death by half among those infected. The trouble with the drug, however, is that its mutagenic powers may also create havoc among other enzymes in the body, including the nucleic acids in our own healthy DNA.
As far back as 1980, researchers have been trying to understand just how damaging NHC, molnupiravir’s metabolite, can be to our own healthy cells. Earlier this year, a study published in the Journal of Infectious Diseases found that the metabolite could indeed be incorporated into and mutate within our host DNA. As others have pointed out, just because something is mutagenic doesn’t mean it’s entirely bad — even sunlight is mutagenic. But, just like sunlight, overexposure can lead to long term ill effects, like cancer. In the case of molnupiravir, the drug may not just lead to the growth of cancerous tumours but also, potentially, to birth defects, either through sperm precursor cells or in pregnant women.
Molnupiravir has been tested for mutagenicity in animals before being moved to human trials, where it is being tested for safety. But that doesn’t mean the drug is fully in the clear. The pool of participants in the clinical trial — around 1,500 patients — is too small to pick up on rare mutagenic events and the early nature of the trial is too short-term to provide a proper view of issues that may occur months, if not years, down the road. Merck would do well to remember their experience with Vioxx, a painkiller that was deemed safe based on initial studies, but later proved deadly.
The FDA originally approved Vioxx based on a safety database that included around 5000 people. Five years later, the drug was recalled after a broader and longer term study found a definitive link between the drug and rare cardiac events. There is evidence that during the time the drug was on the market it may have killed up to 56,000 people and left up to 140,000 with heart disease.
I believe Merck and Ridgeback know there are questions around the possible mutagenicity and teratogenicity of molnupiravir that need to be answered. Both male and female participants in the trial were asked to abstain from sex or use contraception during and shortly after the trial. And reporters have asked the manufacturers about potential mutagenic effects, which Merck has answered by saying that, “the drug will be safe if used as intended and at the concentrations where we have looked and in the concentrations which we are achieving in patients.”
This isn’t the first time a mutagenic drug has been tested for antiviral activity. In that respect, our prior experience with another antiviral drug, favipiravir, may be of interest. It too is an antiviral that targets RNA polymerase, initially developed as a treatment for influenza and, like molnupiravir, now being tested against SARS-CoV-2. The two drugs work in a similar fashion, interchanging two of the four letters of the viral RNA code to create copying errors — molnupiravir switches uracil (U) and cytosine (C), while favipiravir switches guanosine (G) and adenosine (A). Like molnupiravir, favipiravir works by creating enough copying errors during replication to essentially kill off the virus.
The study on mutagenicity of the molnupiravir metabolite in the Journal of Infectious Diseases earlier this year also tested favipirivir. The study found that the molnupiravir metabolite, NHC, was a far more potent mutagen than favipirivir (FAV), which is a drug that has widely known issues related to teratogenicity and links to birth defects.
Because of this, favipiravir has not been approved in the US or the UK, and is only approved in Japan under the strictest of regulations and for the most severe form of influenza, for which no other drugs exist. The challenge with approval of any drug, even under the strictest of regulations, is that once approved it can be used for many purposes, off-label. Favipiravir is already reportedly being distributed and used in Hungary as a treatment for Covid-19, despite no clear evidence of its value and its known risks. This is a danger not just to those receiving the drug, but also — as I wrote about in my previous article on molnupiravir — a danger to all of us, given the potential of drugs like these to supercharge the creation of viral variants.
In November, the FDA will debate the use of molnupiravir only as a treatment for high-risk individuals with mild to moderate disease. But an initial emergency use approval for the drug may lead to unknown harm to all those who receive it. Yesterday, I wrote that if the FDA approves the drug it should be only on a very narrow basis and include a black box warning to emphasize the potential danger of using the drug at suboptimal doses or for large numbers of people for preventive purposes. To that, I add the need for specific warnings for men and women who are actively trying to become pregnant and for women who are already pregnant — under no circumstance should these individuals receive this treatment.
I hope that Merck, Ridgeback, the FDA and the CDC explore the dangers of molnupiravir thoroughly before granting emergency use approval of the drug, especially as other potentially safer antivirals are already on the way. This drug could harm the very people it’s meant to help, those receiving the drug and all of us around them, should new more powerful variants be unleashed.
November 1, 2021
Supercharging New Viral Variants: The Dangers Of Molnupiravir (Part 1)
My next two articles will explore both of these concerns in much greater detail. But let me be very clear right from the start: I am a strong believer in antiviral drugs in general as a means to control the pandemic, having spent much of my early career focused on developing antivirals for the world’s last major pandemic, HIV/AIDS. But I have also spent many years — at Harvard especially where I founded and chaired the Division of Biochemical Pharmacology — studying mutagenesis and the long term effects of damaged DNA.
My concern with molnupiravir is because of the mechanism by which this particular drug works. Molnupiravir works as an antiviral by tricking the virus into using the drug for replication, then inserting errors into the virus’ genetic code once replication is underway. When enough copying errors occur, the virus is essentially killed off, unable to replicate any further. The FDA will soon be debating the safety of molnupiravir for high-risk individuals with Covid-19, something which I will explore in greater detail in my next piece. But my biggest concern with this drug is much larger than the health of any one person, it is molnupiravir’s ability to introduce mutations to the virus itself that are significant enough to change how the virus functions, but not so powerful as to stop it from replicating and becoming the next dominant variant.
In a series of pre-pandemic experiments to determine whether coronaviruses could become resistant to molnupiravir (the answer: yes, they can), researchers tested the active form of molnupiravir against two other highly pathogenic coronaviruses: MERS-CoV and the mouse hepatitis virus (MHV). To identify mutations associated with these phenotypes after passage, the authors sequenced complete genomes of two MHV lineages and two MERS lineages. With MERS, there were up to 41 mutations scattered across the genome. With MHV, there were more than 100 mutations which occurred at every part of the genome.
Overall, the study showed a dose-dependent increase in mutations for both coronaviruses, including in the all important spike protein which is the focus of so much attention today in SARS-CoV-2 variants of concern, like Delta.
Critically, the researchers found that the viruses could survive and replicate to high titers despite such large numbers of mutations in every gene and protein. The viruses tested did show a slight replication disadvantage — though they still replicated to the same high titers, they did so slightly less rapidly compared to the original non-mutated viruses. However, outside of the lab, as the drug is given to millions of people with active infections, this disadvantage may quickly disappear as we would likely provide a prime selection environment to improve the fitness of the virus.
While it’s possible that at the optimal concentration, the drug may very well cause enough mutations to prevent replication and onward transmission of the virus, the impact of suboptimal doses is still very much unknown. The current protocol for the use of molnupiravir is an 800mg dose, given as pills, twice a day for five days. At that concentration, molnupiravir would theoretically take no prisoners, leaving not a single viral genome to escape unscathed. But there is a strong likelihood that in the real world, people will not take the full course of pills. A slew of studies on adherence to daily oral antibiotics suggest that many patients — as many as 40% — fail to complete the full course of treatment. At these suboptimal concentrations, molnupiravir could have the unfortunate effect of introducing mutations across every gene and protein of the virus, including the spike, but not necessarily killing it off.
The drugmakers, Merck and Ridgeback, as well as the FDA are exploring whether molnupiravir is safe for personal use in high-risk individuals with mild to moderate disease and whether its benefits outweigh any potential risks. But they should also be determining the broader danger, and how to prevent the drug from unleashing new and deadlier variants across the globe. Already SARS-CoV-2 has shown a remarkable ability to mutate and survive under pressure. The drug’s manufacturers, Merck and Ridgeback, are entering into licensing deals that would allow the drug to be made and sold widely in more than 105 countries, which means that, if approved by regulators, we will soon have very little control over the drug’s administration and dosages delivered.
We are potentially headed towards a world class disaster. If the FDA does grant approval for the drug — and there is an argument to be made that better and safer antivirals are already on the way — it should be on a very narrow basis and include a black box warning to emphasize the potential danger of using the drug at suboptimal doses or for large numbers of people for preventive purposes. What we know with certainty is that his drug is far from the magic bullet we might hope for with an antiviral for Covid-19. The next article in this two part series will explore the potential risks and dangers of the drug for patients themselves.
September 8, 2021
A Possible Side Effect of Merck's Oral COVID-19 Drug should alarm the Public
A rush for molnupiravir's approval could lead to disaster.
Hydroxychloroquine, which gained EUA usage in 2020 had its EUA rescinded and was demonized over a later discredited study published in the Lancet. Ivermectin, which has been used for decades and showed some possible efficacy against SARS-COV2 infection was castigated, and has recently been labeled as a “horse-dewormer” by the mainstream press to delegitimize the drug. It’s hard to look at the castigation of these decades old drugs that have been administered to millions of people and available over the counter worldwide as anything else than a form of institutional capture.
Now Merck, the pharmaceutical company who held the original patent for Ivermectin, is coming out with a new therapeutic for SARS-COV2 called molnupiravir (I pronounce it as mal-new-pier-ra-vir).
In a press release on June 9th the Biden administration announced that it will spend over $1.2 billion to procure around 1.7 million courses of the drug. Following these numbers this would indicate that a course of molnupiravir could cost around $700, far more than what hydroxychloroquine and Ivermectin would cost (note though, this is not an argument in favor of HCQ or Ivermectin, but bringing awareness to the high cost of this therapeutic). Remember that initial reports of remdesivir indicated a 5 day course of the drug would cost around $3,000 dollars.
Unlike remdesivir, molnupiravir can be administered orally, meaning that it can be used for outpatient treatment as well as a prophylaxis (there does seem to be an orally bioavailable form of remdesivir being developed).
So here we have a large effort to push for an expensive, outpatient therapeutic that can also be used as a prophylaxis. What could go wrong?
Let’s look at how molnupiravir works. To start off, note that molnupiravir IS NOT similar in structure to Ivermectin as many people have claimed. Molnupiravir is a nucleoside analogue, the same class of drugs that remdesivir is in, meaning that it is a modified version of the nucleosides utilized in our bodies.
Molnupiravir is an N-4-hydroxycitidine meaning that there is an -OH group added to the cytosine base.
Molnupiravir (shortened to NHC) acts as a mutagen, meaning that it alters (mutates) the genome of SARS-COV 2. Its mechanism of action first requires it to be inserted into a viral genome during the replication process. Because it looks similar to Cytidine (C) NHC competes with C for insertion into the genome. After being inserted, a second virus cycle must occur. During the next replication cycle a Guanosine (G) could be inserted to base pair with NHC. However, the RNA dependent RNA polymerase (RdRp) may mistake the NHC as a Uracil (U) and add in an Adenosine (A) instead of the correct G. This selective mutation will lead to the downstream production of the wrong proteins. Therefore, unlike other nucleoside analogues that operate to directly stop viral replication, molnupiravir works over several viral replication cycles.
The theory at work here is that continuous incorporation of the wrong base will lead to the accumulation of viral mutations, causing the virus to kill itself off due to the excessive number of accumulated errors, a scenario labeled as a “viral error catastrophe”.
Phase 1 and 2 trials of NHC in mice and ferret models infected with SARS-COV2 showed large improvements, and in human trials there was evidence of no viral load by day 5 of the trial. There were even very few acute toxicities listed.
Although this seems like it could be a wonder drug for SARS-COV2, NHC’s therapeutic capabilities could lead to catastrophic consequences down the road.
Remember that NHC acts as a mutagen and can alter the viral genome. Many nucleoside analogues are broad spectrum therapeutics, meaning that they can affect many cells in your body since our cells are not able to differentiate between the drug and the proper nucleosides.
This side effect is prominent in many cancer patients receiving chemotherapeutics. Many chemotherapeutics are nucleoside analogues, and are administered in an attempt to utilize the rapidly dividing nature of cancer cells, but this also means that many of our rapidly dividing cells can become targets as well. That’s why many of the side effects of chemotherapies include hair loss, dry skin and brittle nails, dry eyes, and GI issues.
In the case of NHC, NHC may be inserted into the genome of noninfected cells, leading to the accumulation of mutations and possibly to the development of cancer.
There is some evidence to suggest this may occur with NHC as indicated by a study by Zhou et. al. 2021 In The Journal of Infectious Disease. In this study the researchers found that exposure to NHC caused a mammalian cell line to mutate and resist cell death when exposed to a toxin, which indicated a gene mutation occurred.
The authors noted:
SARS-CoV2 infection results in an age-related acute respiratory disease spectrum that can be life-threatening, especially in the elderly and individuals with select underlying comorbidies . rNHC has the potential to have therapeutic benefit in this setting. However, there are risks for the host in that the same mutagenic activity that impacts viral replication has the potential for incorporation and mutagenesis of host DNA. This risk can be inferred based on the common intermediate of the ribonucleoside diphosphate shared in the synthesis of both ribonucleoside triphosphates and 2′-deoxyribonucleoside triphosphates. The concern would be that mutations in host DNA could contribute to the development of cancer, or cause birth defects either in a developing fetus or through incorporation into sperm precursor cells…
We take this as evidence that in exposing the viral population to mutagenesis in its RNA form, the host is likely to be exposed in its DNA form. It seems unlikely that a short course of therapy would spare the host from this exposure because both RNA precursors that affect the virus and DNA precursors that would affect the host pass through the common ribonucleoside diphosphate intermediate.
Although NHC is administered as a ribonucleoside, it can be transformed into the deoxynucleoside form and utilized by our own cells, indicated by the mammalian cell culture results, and can lead to mutations and possibly cancer.
This finding should alarm people; here we see the push for a therapeutic where only acute toxicity has been measured with no measurement of long term side effects, that is expected to be dished out to the public in the millions.
Remember that the demonization of HCQ was based on possible cardiac arrhythmias, and in the case of Ivermectin its “lack” of effectiveness, both of which are still up for debate (I will cover the controversy around HCQ in a later article). What seems like very loose standards to target previous drugs that have had a long history of usage is now being ignored when it comes to a brand new drug with very few clinical studies. Again, this isn’t an argument in favor of HCQ or Ivermectin, but points to the hypocrisy of how these drugs are being presented. When some drugs must meet the golden standard of rigorous testing and others can pass by with the bare minimum one has to question what is going on in order to disregard such blatant hypocrisy.
Unfortunately, this has happened previously in regards to remdesivir. When remdesivir was first touted out it was considered a miracle therapeutic in the fight against SARS-COV2, with Dr. Fauci stating that it would be immoral to not provide the drug based on the initial clinical results. Note that in most clinical trials a therapeutic must meet the gold standard of reducing mortality. In the case of remdesivir, the initial clinical trials boasted a reduction of hospital stay from 15 days to 12 days as significant, leading to its widespread adoption. However, it’s now clear that remdesivir is not as effective in treating SARS-COV2 as once claimed. Whether this is due to the timing of remdesivir’s administration or possible adverse reactions, the notion that a $3,000 course of a therapeutic was pushed for while no outpatient therapeutics were available, or demonized, is concerning.
Looking up molnupiravir in the mainstream press you’ll notice that none of them refer to this drug as a “mutagen”, but instead as an RNA polymerase target. This may seem like a game of semantics, but the notion that a drug can act as a possible mutagen, and therefore a carcinogen, and is not being discussed in the mainstream means that millions of Americans may be left uninformed about these possible side effects, and may possibly put themselves at harms risk if they are prescribed this drug.
It is even more concern when we look at the lawsuit against Johnson & Johnson. Johnson & Johnson was recently sued due to the alleged link between their talcum powder and ovarian cancer, a product that has been in mainstream use for decades and is now only just receiving attention about this possible cancer link.
Imagine a drug, dispensed in the millions, to uninformed consumers who may develop cancer years into the future, and the ramifications will be disastrous. With the questionable status of the FDA, and even more widespread skepticism when it comes to previous FDA approved drugs, it is more apparent now than ever of the institutional capture that is at play here.
Of all the drugs that should undergo rigorous testing procedures this should be at the top. Whether or not this occurs is left to be seen, but following with what we’ve seen so far I’ll remain skeptical.
December 23, 2021
Molnupiravir is not authorized for use in patients younger than 18 years of age because molnupiravir may affect bone and cartilage growth. It is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in patients hospitalized due to COVID-19 because benefit of treatment has not been observed in people when treatment started after hospitalization due to COVID-19.
“Today’s authorization provides an additional treatment option against the COVID-19 virus in the form of a pill that can be taken orally. Molnupiravir is limited to situations where other FDA-authorized treatments for COVID-19 are inaccessible or are not clinically appropriate and will be a useful treatment option for some patients with COVID-19 at high risk of hospitalization or death,” said Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research. “As new variants of the virus continue to emerge, it is crucial to expand the country’s arsenal of COVID-19 therapies using emergency use authorization, while continuing to generate additional data on their safety and effectiveness.”
Molnupiravir is not a substitute for vaccination in individuals for whom COVID-19 vaccination and a booster dose are recommended. The FDA has approved one vaccine and authorized others to prevent COVID-19 and serious clinical outcomes associated with a COVID-19 infection, including hospitalization and death. The FDA urges the public to get vaccinated and receive a booster if eligible. Learn more about FDA-approved or -authorized COVID-19 vaccines.
Molnupiravir is a medication that works by introducing errors into the SARS-CoV-2 virus’ genetic code, which prevents the virus from further replicating. Molnupiravir is administered as four 200 milligram capsules taken orally every 12 hours for five days, for a total of 40 capsules. Molnupiravir is not authorized for use for longer than five consecutive days.
The issuance of an EUA is different than an FDA approval. In determining whether to issue an EUA, the FDA evaluates the totality of the scientific evidence available and carefully balances any known or potential risks with any known or potential benefits of the product. Based on the FDA’s review of the totality of the scientific evidence available, the agency has determined that it is reasonable to believe that molnupiravir may be effective for use as treatment of mild-to-moderate COVID-19 in certain adults when alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. The agency has also determined that the known and potential benefits of molnupiravir, when used consistent with the terms and conditions of the authorization, outweigh the known and potential risks of the product. There are no adequate, approved and available alternatives to molnupiravir for the treatment of COVID-19.
The primary data supporting this EUA for molnupiravir are from MOVe-OUT, a randomized, double-blind, placebo-controlled clinical trial studying molnupiravir for the treatment of non-hospitalized patients with mild to moderate COVID-19 at high risk for progression to severe COVID-19 and/or hospitalization. Patients were adults 18 years of age and older with a prespecified chronic medical condition or at increased risk of SARS-CoV-2 infection for other reasons who had not received a COVID-19 vaccine. The main outcome measured in the trial was the percentage of people who were hospitalized or died due to any cause during 29 days of follow-up. Of the 709 people who received molnupiravir, 6.8% were hospitalized or died within this time period compared to 9.7% of the 699 people who received a placebo. Of the people who received molnupiravir one died during the follow-up period compared to nine people who received placebo. Side effects observed in the trial included diarrhea, nausea and dizziness. The safety and effectiveness of molnupiravir for the treatment of COVID-19 continue to be evaluated.
Based on findings from animal reproduction studies, molnupiravir may cause fetal harm when administered to pregnant individuals. Therefore, molnupiravir is not recommended for use during pregnancy. Molnupiravir is only authorized to be prescribed to a pregnant individual after the prescribing healthcare provider has determined that the benefits of being treated with molnupiravir would outweigh the risks for that individual patient and after the prescribing health care provider has communicated the known and potential benefits and the potential risks of using molnupiravir during pregnancy to the pregnant individual. Females of childbearing potential are advised to use a reliable method of birth control correctly and consistently during treatment with molnupiravir and for four days after the final dose. Males of reproductive potential who are sexually active with females of childbearing potential are advised to use a reliable method of birth control correctly and consistently during treatment with molnupiravir and for at least three months after the final dose. Questions and concerns about reliable birth control methods that are appropriate for use during treatment with molnupiravir, as well as how molnupiravir may affect sperm cells, should be directed at one’s healthcare provider.
Under the EUA, fact sheets that provide important information about using molnupiravir in the treatment of COVID-19 as authorized must be made available to healthcare providers and to patients and caregivers. These fact sheets include dosing instructions, potential side effects and information about who is able to prescribe molnupiravir