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The FDA’s panel is rigorously approving Merckpill, despite its reduced effectiveness

Tuesday’s Food and Drug Administration Advisory Board Merck Ridgeback Biotherapeutics’ oral Covid treatment, despite questions about the drug’s efficacy, safety, and whether the virus helps mutate into more dangerous variants.

The FDA’s Antimicrobial Advisory Board voted 13:10, recommending urgent approval of molnupiravir. Molnupiravir was first welcomed as a potential game changer in the fight against Covid because it can be taken at home rather than in the hospital like other treatments. It is designed to treat adults with mild to moderate symptoms of Covid-19, who are at high risk of severe illness. 800 milligrams of pills are taken every 12 hours for 5 days after the onset of symptoms.

This drug requires final approval from the FDA and the US Centers for Disease Control and Prevention before it is released to the public in an emergency. The FDA does not have to accept the panel’s advice, but it often does.

Many members of the advisory board explained that voting is difficult. The vote required careful consideration of the risks and benefits of the drug that raises unanswered questions, but was able to help adults at risk of severe Covid.

Merck initially stated that the drug was more than 50% effective in preventing hospitalization and death, but more complete data presented to the FDA on Tuesday stated that the drug was only 30% effective. I am.

Neither the FDA nor Merck recommends using this drug for children and pregnant women. Molnupiravir has been found to be fatal to embryos in pregnant rats, causing birth defects and reducing fetal weight. The data also show that it also caused other defects that impede bone growth in young puppies, along with other abnormalities.

Molnupiravir works by promoting a virus that mutates Covid and produces errors that impede its ability to replicate and spread. However, some doctors and scientists were worried that the virus could mutate in ways that would reduce the effectiveness of vaccines and treatments.

“Even with a very low probability of 1 in 10,000 or 1 in 100,000, this drug can induce an escape variant from a vaccine that we do not cover, which is actually Can be devastating to the whole world, “CEO Dr. James Hilldress, Dean of Meharry Medical College in Nashville, Tennessee, told the panel.

Nicholas Cartsonis, senior vice president of clinical research at Merck, said the company has no data on the potential for such mutations. However, Kartsonis noted that there was no increase in the rate of abnormal changes to the pesplomer used by the virus to attach to human cells compared to the placebo group in clinical trials. Hildress told Merck that it was Merck’s duty to estimate the potential for escape mutants.

“We are exploring the feasibility of sequencing databases using the publicly available SARSCoV-2 currently available and monitoring the emergence of these novel variants in replicase complexes and peplomers,” Kartsonis said. Says.

Patrick Harrington, FDA’s senior virology reviewer, said it is unclear whether changes in peplomer associated with molnupiravir could have a substantially more widespread effect on viral evolution.

“In order for molnupiravir to affect the evolution of Sars-CoV-2 beyond treated individuals, the mutant must also be contagious, and at this time it is unclear if this is to a large extent possible. “Hmm,” Harrington told the panel.

Merck I submitted an application October for the FDA to approve Molnupiravir in an emergency. So far, no oral antiviral drug has been approved to treat Covid. Pfizer is seeking approval as well For itself Oral Covid remedy The popular HIV drug is said to be 89% effective in preventing hospitalization and death.

In its initial application and presentation to the FDA Advisory Board on Tuesday, Merck stated in an interim analysis of 762 patients that pills are 50% effective in reducing the risk of hospitalization or death. However, according to the company, an analysis of the total population of about 1,400 participants showed a low efficacy rate of 30%.

In an interim analysis of 646 participants, hospitalizations and deaths were actually higher in 6.2% of the pill-treated group compared to 4.2% of the placebo group who did not take the drug.

Kartsonis told the FDA committee that the reduction in hospitalization and mortality in the placebo group compared to the group taking molnupirivar was “not totaled.”

“The second part of the study was after the interim analysis enrolled older people and older, more diabetic patients,” Kartsonis said. “You would have expected it to happen — you will see more mortality.”

“But there are more women in the second part of the study, which is associated with lower risk and an increase in antibody-positive patients,” he said.

Participants in the study were unvaccinated at high risk of severe Covid because they were over 60 years old or had pre-existing conditions such as diabetes, obesity, kidney disease, severe heart disease, lung disease, and cancer. Was an adult.

Kartsonis told the FDA Advisory Board, based on an interim analysis of 762 participants, molnupiravir significantly reduced the risk of hospitalization or death during clinical trials, with 9 out of 10 deaths occurring in the placebo group. Said he did not take any medication.

According to Kartsonis, Merck did not identify any safety concerns associated with molnupiravir during clinical trials. He said a few patients experienced diarrhea, nausea and dizziness.

“Currently, more than 50,000 Americans in our hospital are suffering from the disease, and another surge in the coming months of winter, as new changes in concern may occur. Is imminent, “said Kartsonis. “We are in desperate need of a new, effective, well-tolerated and convenient treatment to treat COVID 19 in an outpatient setting,” he added.

In a briefing prepared for the Commission, FDA scientists said animal studies have discovered that the drug can lead to fetal weight loss and abnormal bone formation. Merck did not intend to use molnupiravir in pregnant women and did not include it in clinical trials.

Mark Seaton, head of research at the FDA’s Department of Pharmacology and Toxicology, said that rat fetal eye, kidney and skeletal malformations harm the human fetus when molnupiravir is administered to pregnant women. He told the advisory board that it showed the possibility. However, according to Seaton, the abnormal bone and cartilage formation observed in animals is not believed to be relevant to adult humans.

Dr. Janet Kragin, Head of Health for Congenital Defects at the CDC, said prescribing molnupiravir during pregnancy is unethical given the potential side effects, but for pregnant women suffering from Covid. Rejecting medicine is also a problem.

“I don’t know if I can ethically tell pregnant women who have Covi-19 that they can’t take the drug if they decide they need it,” Cragin said, her view. He said it did not represent the CDC.

“Pregnancy itself can be seen as a risk factor for the progression to severe Covid’s disease,” she said. “We know that respiratory illnesses are becoming more severe and can be life-threatening as pregnancy progresses. That certainly applies to Covid.”

Dr. Hildress, CEO of Meharry Medical College, was clear on his opposition.

“Do you want to use this drug to reduce the risk of harm to your mother by 30% while exposing your embryos and foetations to a much higher risk of harm? And my answer is no,” Hildress said. .. “And there is no situation where I advise pregnant women to take this medicine.”

Robert Heflich, Head of Genetics and Molecular Toxicology at the FDA, said molnupiravir modified human genes in clinical practice, given that molnupiravir clearly did not show mutagenicity during studies in rodents. He said the risk of doing so was low. According to Merck, the study did not show an increase in mutation frequency in the rodent liver or bone marrow.

However, this study was conducted as a follow-up to previous studies using rodents that were not definitive as to whether molnupiravir was mutagenic. Molnupiravir was found to be mutagenic during an in vitro study using bacteria and hamster cells.

Data on whether molnupiravir is associated with gene mutations was the source of controversy in the public comments section of the conference. Some experts and the general public have expressed concern that a single study is the basis for conclusions on potential human risks. However, FDA experts said they believe the risk of gene mutations is low given the short five-day treatment period for molnupiravir.

The FDA’s panel is rigorously approving Merckpill, despite its reduced effectiveness The FDA’s panel is rigorously approving Merckpill, despite its reduced effectiveness

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