FDA authorization of Merck COVID pill called "worst decision in its history"
By Rich Haridy
December 23, 2021
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
The US Food and Drug Administration (FDA) has issued emergency use authorization to a second oral COVID-19 treatment. Called molnupiravir the new drug is not as effective as Pfizer’s recently approved COVID antiviral pill, and many experts suggest the FDA should never have authorized it in the first place as it has the potential to generate new SARS-CoV-2 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.
The US Food and Drug Administration (FDA) has issued emergency use authorization to a second oral COVID-19 treatment. Called molnupiravir the new drug is not as effective as Pfizer’s recently approved COVID antiviral pill, and many experts suggest the FDA should never have authorized it in the first place as it has the potential to generate new SARS-CoV-2 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.
Michael Lin, PhD-MD DNA
@michaelzlin
Dec 23
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://fda.gov/news-events/pr
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.
9:53 AM · Dec 23, 2021
271 Likes
https://twitter.com/michaelzlin/status/1474030344328204288 (scroll down)
“The worst case scenario that we haven’t ruled out is MOV [molnupiravir] will lead to years of new variants, with people desperately taking it to fight the new variants that it spawns, creating a vicious positive feedback loop while causing countless suffering and deaths,” Lin writes on Twitter. “Isn't that grim enough to delay this decision until Merck convincingly tells us how many functional mutants are created and transmitted per every 1000 patients to their family members for example?”
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.”
Source: FDA
https://newatlas.com/health-wellbeing/fda-mer...de-effect/
By Rich Haridy
December 23, 2021
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
The US Food and Drug Administration (FDA) has issued emergency use authorization to a second oral COVID-19 treatment. Called molnupiravir the new drug is not as effective as Pfizer’s recently approved COVID antiviral pill, and many experts suggest the FDA should never have authorized it in the first place as it has the potential to generate new SARS-CoV-2 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.
The US Food and Drug Administration (FDA) has issued emergency use authorization to a second oral COVID-19 treatment. Called molnupiravir the new drug is not as effective as Pfizer’s recently approved COVID antiviral pill, and many experts suggest the FDA should never have authorized it in the first place as it has the potential to generate new SARS-CoV-2 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.
Michael Lin, PhD-MD DNA
@michaelzlin
Dec 23
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://fda.gov/news-events/pr
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.
9:53 AM · Dec 23, 2021
271 Likes
https://twitter.com/michaelzlin/status/1474030344328204288 (scroll down)
“The worst case scenario that we haven’t ruled out is MOV [molnupiravir] will lead to years of new variants, with people desperately taking it to fight the new variants that it spawns, creating a vicious positive feedback loop while causing countless suffering and deaths,” Lin writes on Twitter. “Isn't that grim enough to delay this decision until Merck convincingly tells us how many functional mutants are created and transmitted per every 1000 patients to their family members for example?”
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.”
Source: FDA
https://newatlas.com/health-wellbeing/fda-mer...de-effect/
