An advisory panel to the U.S. Food and Drug Administration voted to grant emergency authorization to Merck’s oral COVID-19 pill molnupiravir (Lagevrio) — but only by a narrow margin.1 The 13-to-10 vote speaks volumes about the panel’s confidence in the treatment, as do the numerous concerns regarding efficacy and safety voiced by the panel.
Merck reported in a press release in October 2021 that their antiviral drug led to a 50% risk reduction in hospitalization and death among COVID-19 patients. That was based on data from 386 patients, however. When the full analysis was released, which included data from 710 patients, the effectiveness declined significantly.
Among those who received the drug, the rate of all-cause hospitalization or death was 6.8%, compared to 9.7% in the placebo group — a relative risk reduction of just 30%.2 Several panelists reportedly said that the change in data was poorly explained,3 and it represents just one concern voiced by experts that raise major red flags about Merck’s COVID-19 pill.
Placebo Outperformed Drug in Second Half of Trial
In an addendum released November 22, 2021, the FDA stated that they became aware of the “topline safety and efficacy results from all 1,433 randomized participants.”4 The data showed that patients taking the placebo fared better than those taking molnupiravir.
As noted in a commentary in the BMJ, “The full data showed more hospital admissions among patients taking molnupiravir (6.2%) than among those taking a placebo (4.7%) and led Merck to revise the benefit of preventing admission downwards to 30%.”5
Further, the trial was stopped early after interim results showed eight deaths in the placebo group compared to zero in the molnupiravir group. However, post-interim results painted a very different picture — one death was recorded in each group.6 The BMJ reported:7
“When questioned why the trial’s later participants showed such different outcomes than those in the interim analysis, a physician representing Merck told the panelists that the later group contained older patients, were more likely to be female and recruited from Europe, and more likely to carry the delta variant. But, he said, the drop in efficacy at the end of the trial ‘doesn’t really add up to us.’”