U.S. allows Merck’s COVID-19 pill amid safety, variant concerns | Science

The U.S Food and Drug Administration (FDA) on Thursday authorized another new pill to treat the Omicron variant, this time from Merck.

While Pfizer’s antiviral may prove to be more effective, and Merck’s pill has left some scientists questioning the dangers behind its mechanism of action, molnupiravir will be another weapon in the armamentarium of COVID-19 treatments for the U.S. in a time of need, as two monoclonal antibody (mAb) treatments from Regeneron and Eli Lilly are no longer effective against Omicron, and as supplies of a third mAb from Vir/GlaxoSmithKline are very limited.

Supplies of the Merck pill will not be as limited, as the U.S. may have about 400,000 courses of Merck’s pill available in the next few days, and by the end of January, the U.S. government expects to have about 3 million courses of Merck’s pill, which is the entire order that the U.S. made.

The concern with Merck’s pill is that it works by inhibiting SARS-CoV-2 replication through viral mutagenesis, and some scientists have raised serious reservations about that mechanism of action.

FDA’s Antimicrobial Drugs Advisory Committee narrowly voted 13-10 last month in favor of the pill’s benefits outweighing the risks for adults within 5 days of developing COVID-19 symptoms.

“Committee members who voted ‘No’ cited the following as reasons for concluding that the overall benefit-risk ratio was unfavorable: 1) a high number-needed-to-treat compared with placebo, 2) unclear efficacy against the Delta variant, 3) potential to drive viral mutations, and 4) mutagenicity risks,” according to a summary of the meeting.

Merck has to provide reports to FDA on a monthly basis summarizing any findings as a result of its monitoring activities of genomic database(s) for the emergence of global viral variants.

As part of Thursday’s authorization, FDA made clear that it should be provided to those “for whom alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate,” meaning that if Pfizer’s pill is available, that might be a better option.

“I don’t think you would find anyone who would prefer the Merck pill to the Pfizer pill, given the data evident so far,” Walid Gellad, a professor of medicine at the University of Pittsburgh, told Endpoints News previously.

As part of the emergency use authorization, FDA said Merck has to “conduct a thorough investigation into the differences in efficacy observed in the first and second half” of its pivotal trial. Panelists at the adcomm last month centered their questioning on the cause of this drop-off in preventing hospitalizations and deaths, from 50% to 30% between interim and final results. Merck and FDA offered few specifics at the meeting on why the efficacy declined.

Unlike the Pfizer pill, FDA also warned Thursday that molnupiravir is not recommended for use during pregnancy, as based on findings from animal reproduction studies, molnupiravir may cause fetal harm.

Merck must maintain a pregnancy surveillance program to collect information on individuals who are exposed to molnupiravir during pregnancy. FDA also said that sexually active individuals with partners of childbearing potential are advised to use contraception during molnupiravir treatment and for at least 3 months after the last dose.

Molnupiravir is also not authorized for use in patients who are less than 18 years of age, or for use for longer than 5 consecutive days. A course of treatment is administered as four 200 milligram capsules taken orally every 12 hours for 5 days, for a total of 40 capsules.