An advisory panel to the U.S. Food and Drug Administration (FDA) voted in favor of emergency approval of Merck’s oral COVID-19 drug molnupiravir (Lagevrio) – but only by a narrow majority.
Major Doubts About Merck’s COVID-19 Pill
The 13-10 vote speaks volumes about the panel’s confidence in the treatment, as well as the many concerns about efficacy and safety that the panel had raised.
In October 2021, Merck reported in a press release that the antiviral drug led to a 50 percent reduction in the risk of hospitalizations and deaths among COVID-19 patients. However, this was based on data from 386 patients. When the full analysis was published, which included data from 710 patients, efficacy declined significantly.
Among patients who received the drug, the overall rate of hospitalization or death was 6.8%, compared with 9.7% in the placebo group – a relative risk reduction of only 30%. Several panelists said the change in data was poorly explained, and this is just one of the concerns raised by experts that cast major doubt on Merck’s COVID-19 pill.
Placebo Outperformed the Drug in the Second Half of the Study
In an addendum published Nov. 22, 2021, the FDA said it learned of “top-line safety and efficacy results for all 1433 randomized participants.” The data showed that patients taking the placebo did better than those receiving molnupiravir.
According to a commentary in the BMJ, “The full data showed that patients taking molnupiravir were more likely to be hospitalized (6.2%) than patients taking placebo (4.7%), leading Merck to revise the benefit of preventing hospitalizations downward to 30%.”
In addition, the trial was stopped early after interim results showed eight deaths in the placebo group compared with zero in the molnupiravir group. However, results after the interim review showed a very different picture – one death was recorded in each group. The BMJ reported:
When asked why the later study participants showed such different results compared with the interim analysis, a physician representing Merck told the panelists that the later group included older patients who were more likely to be female, recruited from Europe, and more likely to carry the delta variant. But, he said, the decline in efficacy at the end of the study doesn’t really make sense to us.
Dr. Pierre Kory, who is part of the group that founded the Front Line COVID-19 Critical Care Working Group (FLCCC) to advance early treatment of COVID-19, has implored the U.S. government to review the extensive data on the drug ivermectin to prevent COVID-19 from progressing in patients with early symptoms and to aid the recovery of critically ill patients – to no avail.
Nevertheless, the FDA granted Merck’s highly questionable drug an emergency use authorization (EUA). Kory tweeted his dismay at the decision:
No LOVE for pharma given its unconscionable behavior now and in the past. But I can HOPE. Hope now dashed: half of Merck’s study: placebo outperforms drug. Ouch. Even the FDA admits the drug is weak and risky…and approves it anyway? EUA for IVM [ivermectin] please.
Fauci: Merck’s COVID Pill ‘Impressive’
In October, Dr. Anthony Fauci praised molnupiravir as “extremely important” and lauded its results to date. “It is a pill that is administered by mouth, so you don’t need anything special except to take a pill, as you do with any pill. And the results are really quite impressive,” he said on CNN’s “State of the Union.”
It’s unclear whether Fauci has changed his mind in light of the less-than-stellar results now available, but the U.S. government has already purchased about 3.1 million pills at a cost of about $2.2 billion. Officials have touted the simplicity of the pill, which is taken orally at home every 12 hours for five days.
Merck plans to produce 10 million packs of the drug by the end of 2021, but the FDA panel’s support for the drug is even stranger considering that more effective treatment options – namely monoclonal antibodies – have already been approved. As noted in BMJ:
The U.S. has already approved three monoclonal antibody cocktails that have shown greater than 60% efficacy in preventing uptake, and the FDA generally does not approve drugs that are less effective than those already in use.
Red Alert: Molnupiravir Causes Viral Mutations
Not only the drug’s effectiveness, but also its safety was a concern for some of the FDA panels. Molnupiravir works by inserting itself into the genetic material of the virus and causing mutations that ultimately kill the virus. However, a pill that triggers mutations in a virus could also trigger mutations in mammalian cells, posing risks of cancer and birth defects.
The risks are so severe that the drug is recommended only for adults because it could be dangerous for growing children. Animal studies have shown greater thickening of the growth plates, among other effects. Pregnant women and those expecting pregnancy were excluded from the trials, and male subjects were not allowed to donate sperm for one month after the last dose. Modern Discontent reported:
People should be reminded of the problem with thalidomide in the 1960s, a drug used to treat morning sickness in pregnant women that scientists later found was teratogenic and caused many birth defects. For this reason, molnupiravir should not be used in pregnant women under any circumstances due to concerns about possible teratogenicity.
Ultimately, the FDA panel recommended that the drug not be approved for children or nursing mothers because of the risks of embryo-fetal toxicity, bone and cartilage toxicity, and mutagenicity.
Molnupiravir Could Trigger Escape Mutants
Molnupiravir’s mechanism of action – driving genetic mutations – is problematic in itself, considering that the coronavirus spike protein is already mutating rapidly. During Merck’s Phase II trial, the SARS-CoV-2 spike protein had 72 structural nucleotide changes, while the spike protein in the placebo group had only nine such changes.
Some of these changes could make the virus more infectious, make it resistant to vaccines and treatments, and release escape mutants into the environment. James Hildreth, a member of the FDA panel and president of Meharry Medical College in Tennessee, voted against approving molnupiravir for that reason.
He said, “Even if there is a very small chance, 1 in 10,000 or 100,000, that this drug will cause an outbreak mutant that is not covered by existing vaccines, that would be catastrophic for the whole world.” William Haseltine, who founded and chaired the Department of Biochemical Pharmacology at Harvard, expressed similar concerns in Forbes, stating:
My concerns are based on two main aspects. The first is the potential mutagenicity of the drug and the possibility that its use could lead to birth defects or cancerous tumors. The second is a far greater and potentially more deadly danger: the drug’s potential to amplify SARS-CoV-2 mutations and unleash an even more virulent variant on the world.
We are heading for a ‘World-Class Catastrophe’
Haseltine explained that molnupiravir was tested in pre-pandemic studies against pathogenic coronaviruses such as MERS-CoV. Not only were the coronaviruses able to become resistant to the drug, but the viruses survived and continued to replicate with a large number of mutations in all genes and proteins.
In the laboratory, the treated viruses replicated somewhat more slowly than the untreated viruses; however, in the real world, the drug is likely to cause harm in unintended ways, especially since many people do not stop taking the entire drug.
At suboptimal doses, that is, if someone doesn’t take the drug for the entire five days or skips a few doses here and there, it can create the best conditions for mutant viruses to be transmitted. Haseltine told Forbes:
It is very likely that people in the real world will not take the entire tablet. A number of studies on adherence to daily oral antibiotics show that many patients – as many as 40% – do not complete the full course of treatment.
At these suboptimal concentrations, molnupiravir could have the unfortunate effect of causing mutations in all the genes and proteins of the virus, including the spike, but not necessarily killing it.
Drug makers Merck and Ridgeback, as well as the FDA, are investigating whether molnupiravir is safe for personal use in high-risk people with mild to moderate disease and whether its benefits outweigh any potential risks.
But they should also determine the broader dangers and how to prevent the drug from releasing new and more deadly variants around the world. SARS-CoV-2 has already shown a remarkable ability to mutate and survive under pressure.
The drug’s manufacturers, Merck and Ridgeback, are in the process of entering into licensing agreements that would allow the drug to be manufactured and sold in more than 105 countries, which means that if it is approved by regulators, we will soon have very little control over the administration of the drug and the doses administered. We may be heading for a world-class disaster.
Are there other Options?
There are early treatment options for COVID-19 that could save lives, but they are not widely promoted in the media. Dr. Peter McCullough recommends seeking early treatment if you have COVID-19, whether or not you have received the vaccine.
McCullough’s early treatment initially includes a food bundle of zinc, vitamin D, vitamin C and quercetin. While recovering at home, open windows and provide adequate fresh air and ventilation. If symptoms persist or worsen, he recommends seeing a doctor and requesting monoclonal antibody therapy.
Treatment down the road includes anti-infectives such as HCQ or ivermectin, antibiotics, steroids, and blood thinners. If your doctor refuses to treat early-stage COVID-19, you should find a new one and/or visit a telemedicine clinic that can help you because “the preclinical phase is the time of therapeutic opportunity.” You can also download “A Guide to Home-Based COVID Treatment” by McCullough and colleagues.
FLCCC’s I-MASK+ protocol can also be downloaded in its entirety and includes step-by-step instructions for preventing and treating the early symptoms of COVID-19. FLCCC also has protocols for prevention and early home treatment called I-MASS, which includes ivermectin, vitamin D3, a multivitamin, and a digital thermometer for monitoring body temperature during the prevention phase, as well as ivermectin, melatonin, aspirin, and antiseptic mouthwash for early home treatment.
Households or close contacts of COVID-19 patients can take ivermectin (18 milligrams, then repeat dose in 48 hours) for post-exposure prophylaxis. Their protocols are being translated into 23 different languages to provide widespread, free access to this life-saving information, including how to obtain ivermectin, which FLCCC hopes will be formally incorporated into national or international COVID-19 treatment guidelines in the near future.