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In a 13-to-10 vote, advisors for the Food and Drug Administration narrowly supported authorizing Merck's Thor-inspired antiviral pill molnupiravir for use against severe COVID-19.
The FDA's panel of advisors—the Antimicrobial Drugs Advisory Committee (AMDAC)—struggled in an all-day meeting Tuesday to weigh the drug's risks, its modest benefits, and the limited available data. The latest analysis suggests that the pill is only 30 percent effective at preventing hospitalization and death from COVID-19 in people at high risk of severe disease. Meanwhile, the drug has the worrisome potential to cause mutations, leading advisors to agonize over whether it should be offered to pregnant people.
Molnupiravir's final data and today's vote is a significant disappointment from the early fanfare around the drug, which initially promised to be an easy-to-use oral drug to effectively prevent severe COVID-19. "Our prediction from our in vitro studies and now with this data is that molnupiravir is named after the right [thing]... this is a hammer against SARS-CoV-2 regardless of the variant," Merck’s head of research and development, Dean Li, said last month.
At the time, Merck and its partner, Ridgeback Biotherapeutics, had put out a press release trumpeting that the antiviral pill appeared to cut the risk of hospitalization and death from COVID-19 by about 50 percent in infected people at risk of severe disease. The result came from an interim analysis involving 762 people who were followed for about a month after testing positive. In the placebo group, Merck reported that 53 of 377 people were hospitalized with COVID-19, and eight died. Among 386 people who received the drug, only 28 were hospitalized, and none of those patients died. Comparing the two groups, the rate of hospitalization and death in the placebo group was 14.1 percent versus only 7.3 percent in the molnupiravir group.
But since that analysis, Merck collected data from an additional 646 people—and in this batch of people, the benefit of molnupiravir disappeared. Of 322 people in the placebo group, 15 were hospitalized and one died. That is, the rate of hospitalization and death was about 4.7 percent with a placebo. Of 324 people who received molnupiravir, 20 were hospitalized and one died. That's a rate of hospitalization and death of 6.2 percent, which is slightly higher than the rate in the placebo group.
For the final analysis, Merck combined the two batches, concluding that molnupiravir was 30 percent effective overall at preventing hospitalization and death. Of the 699 people total who received a placebo, 68 were hospitalized and nine died. Of the 710 people total who received molnupiravir, 48 were hospitalized and one died. The rates of hospitalization and death worked out to 9.7 percent in the placebo group compared with 6.8 percent in the molnupiravir group, suggesting the drug led to a 3 percent decrease in absolute risk and a 30 percent decrease in relative risk.
Members of the FDA panel summarized the efficacy data as "not overwhelmingly good" and "modest at best."
Though there were no safety concerns from either batch of trial data, FDA reviewers agonized over unknowns about the drug's possible mutagenic effects. Molnupiravir works to sabotage SARS-CoV-2 by acting as a decoy building block for the virus' genetic code. But, with that strategy, there's also the potential it could disrupt the genetic code of humans. AMDAC members largely felt that Merck had not done enough safety monitoring to better understand the risk of mutations in people, particularly in pregnant people.
In the end, the committee was split by the urgent need for new drugs to reduce COVID-19 deaths and the marginal benefits and concerning risk that this drug in particular offers. In final remarks, many advisors said their ultimate vote was a difficult decision and called for more data. Some who voted yes outlined narrow scenarios where they could support the drug's use, namely in very high-risk, nonpregnant, unvaccinated people who understand the risks of the drug and would make sure to take it as directed.
Following the close vote and many expressions of concern, the FDA will now decide if it will issue an emergency use authorization for molnupiravir. The regulator tends to follow the advice of its advisory panels.
In addition to molnupiravir, the FDA will also be reviewing an antiviral pill from Pfizer, which the company says is 89 percent effective against hospitalization and death from COVID-19. Pfizer noted that its drug carries no risk of mutations.
https://arstechnica.com/science/2021...exing-experts/
The FDA's panel of advisors—the Antimicrobial Drugs Advisory Committee (AMDAC)—struggled in an all-day meeting Tuesday to weigh the drug's risks, its modest benefits, and the limited available data. The latest analysis suggests that the pill is only 30 percent effective at preventing hospitalization and death from COVID-19 in people at high risk of severe disease. Meanwhile, the drug has the worrisome potential to cause mutations, leading advisors to agonize over whether it should be offered to pregnant people.
Molnupiravir's final data and today's vote is a significant disappointment from the early fanfare around the drug, which initially promised to be an easy-to-use oral drug to effectively prevent severe COVID-19. "Our prediction from our in vitro studies and now with this data is that molnupiravir is named after the right [thing]... this is a hammer against SARS-CoV-2 regardless of the variant," Merck’s head of research and development, Dean Li, said last month.
At the time, Merck and its partner, Ridgeback Biotherapeutics, had put out a press release trumpeting that the antiviral pill appeared to cut the risk of hospitalization and death from COVID-19 by about 50 percent in infected people at risk of severe disease. The result came from an interim analysis involving 762 people who were followed for about a month after testing positive. In the placebo group, Merck reported that 53 of 377 people were hospitalized with COVID-19, and eight died. Among 386 people who received the drug, only 28 were hospitalized, and none of those patients died. Comparing the two groups, the rate of hospitalization and death in the placebo group was 14.1 percent versus only 7.3 percent in the molnupiravir group.
But since that analysis, Merck collected data from an additional 646 people—and in this batch of people, the benefit of molnupiravir disappeared. Of 322 people in the placebo group, 15 were hospitalized and one died. That is, the rate of hospitalization and death was about 4.7 percent with a placebo. Of 324 people who received molnupiravir, 20 were hospitalized and one died. That's a rate of hospitalization and death of 6.2 percent, which is slightly higher than the rate in the placebo group.
For the final analysis, Merck combined the two batches, concluding that molnupiravir was 30 percent effective overall at preventing hospitalization and death. Of the 699 people total who received a placebo, 68 were hospitalized and nine died. Of the 710 people total who received molnupiravir, 48 were hospitalized and one died. The rates of hospitalization and death worked out to 9.7 percent in the placebo group compared with 6.8 percent in the molnupiravir group, suggesting the drug led to a 3 percent decrease in absolute risk and a 30 percent decrease in relative risk.
Members of the FDA panel summarized the efficacy data as "not overwhelmingly good" and "modest at best."
Though there were no safety concerns from either batch of trial data, FDA reviewers agonized over unknowns about the drug's possible mutagenic effects. Molnupiravir works to sabotage SARS-CoV-2 by acting as a decoy building block for the virus' genetic code. But, with that strategy, there's also the potential it could disrupt the genetic code of humans. AMDAC members largely felt that Merck had not done enough safety monitoring to better understand the risk of mutations in people, particularly in pregnant people.
In the end, the committee was split by the urgent need for new drugs to reduce COVID-19 deaths and the marginal benefits and concerning risk that this drug in particular offers. In final remarks, many advisors said their ultimate vote was a difficult decision and called for more data. Some who voted yes outlined narrow scenarios where they could support the drug's use, namely in very high-risk, nonpregnant, unvaccinated people who understand the risks of the drug and would make sure to take it as directed.
Following the close vote and many expressions of concern, the FDA will now decide if it will issue an emergency use authorization for molnupiravir. The regulator tends to follow the advice of its advisory panels.
In addition to molnupiravir, the FDA will also be reviewing an antiviral pill from Pfizer, which the company says is 89 percent effective against hospitalization and death from COVID-19. Pfizer noted that its drug carries no risk of mutations.
https://arstechnica.com/science/2021...exing-experts/
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