Ahead of a U.S Food and Drug Administration advisory panel meeting, drugmaker Merck has revealed final analysis data from a Phase 3 trial testing its oral antiviral pill against COVID-19. The new data reveals the treatment is significantly less effective than early indications.
Two months ago, Merck announced promising early data for molnupiravir, its oral antiviral COVID-19 treatment. The interim Phase 3 trial analysis revealed the pill reduced a person’s risk of hospitalization or death from COVID-19 by 50 percent when taken within five days of symptoms appearing.
However, the final trial analysis is now indicating the treatment is much less effective than first suggested. The new data, encompassing all the Phase 3 trial participants (1,433 subjects, instead of the earlier analysis that only looked at 775 subjects), found 9.7 percent of those in the placebo group experienced either hospitalization or death from COVID-19 compared to 6.8 percent in the group taking the new antiviral.
This means molnupiravir reduces a person's risk of hospitalization or death from COVID-19 by 30 percent, and not 50 percent, as was previously reported after the interim analysis. The new data also reports nine COVID-19 deaths were seen in the placebo group, compared to just one death in the molnupiravir group.
The new data comes ahead of this week’s Antimicrobial Drugs Advisory Committee (ADAC) meeting. The ADAC is an independent panel that publicly convenes to issue antimicrobial drug approval recommendations, and while the FDA generally follows ADAC’s advice, it is not compelled to do so.
Alongside evaluating the molnupiravir trial data, the FDA has issued two key questions for ADAC to discuss. One question asks if there should be any monitoring strategies put in place to track viral mutations that may be triggered through the use of molnupiravir.
Molnupiravir inhibits the replication of SARS-CoV-2 by increasing the frequency of viral RNA mutations. This essentially floods the viral genome with so many errors the virus can no longer effectively replicate. The FDA’s question to ADAC is linked to some concerns that widespread use of molnupiravir could hasten the rise of dangerous SARS-CoV-2 variants.
The other key question the FDA is asking ADAC to consider is whether molnupiravir is safe for pregnant women. Hypothetically, mutagenic drugs such as molnupiravir could generate birth defects. Pregnant women were excluded from Merck’s Phase 3 trial of molnupiravir, so the FDA is tasking ADAC with providing recommendations for what groups of people should be excluded from using the drug.
No serious adverse effects were detected in Merck’s molnupiravir trial and it is likely the antiviral will be issued an Emergency Use Authorization by the FDA despite this reduced efficacy.
This will make it the first oral treatment designed specifically for COVID-19 to be approved for clinical use. Hot on its heels is a COVID-19 antiviral pill from Pfizer, which recently reported extraordinary interim results of reducing hospitalization or death in high-risk patients by 89 percent compared to placebo.
Source: Merck