The FDA convenes an advisory committee on Tuesday to review the company’s antiviral pill, molnupiravir. But the discussion will highlight the drug’s limitations, including safety risks and limited efficacy, which could lower expectations for the drug’s long-term sales even further.
Analysts widely expect the agency to authorize molnupiravir, although authorization is likely limited.
Shares of Merck (ticker: MRK) fell even as shares of Covid-19 vaccine makers soared on Friday and Monday against the backdrop of the emergence of a disturbing new variant of Covid, Omicron.
Merck stock fell 3.8% on Friday and 5.8% on Monday, while the S&P 500 rose 1.5%. Merck was the worst performer on the S&P 500 on Monday.
The drop came as hopes for molnupiravir faded. Shares jumped 8.4% on October 1, when Merck announced that initial data showed the drug reduced the risk of hospitalization or death by about 50%; Stocks of Covid-19 vaccines had fallen. Since then, the shine of the antiviral pill has faded.
First of all,
(PFE) has announced what appears to be more positive data on its Covid-19 antiviral, known as Paxlovid. Then on Friday, Merck said the updated results from its Phase 3 study of molnupiravir are much less promising than initial data showed. The study, according to the company, showed that molnupiravir reduced the risk of hospitalization or death by 30%, not the initial result by about 50%.
Early Monday, Citigroup analyst Andrew Baum downgraded his Merck rating to Buy Neutral, partly citing new risks to molnupiravir sales estimates.
âLagevrio’s clinical profile continues to deteriorate,â Baum wrote, referring to molnupiravir by the name under which it is marketed in the UK, where it already has regulatory approval.
A spokesperson for Merck said the company is not commenting on analysts’ reports or recommendations.
Beginning of October, Barron reports concerns raised by some scientists that molnupiravir may increase the risk of cancer or birth defects. These concerns persist, although Merck maintains that its preclinical studies show the drug to be safe.
The concerns stem from how molnupiravir inhibits the replication of the virus that causes Covid-19: first by incorporating itself into the genetic code of the virus, and then causing errors as the virus replicates. The concern is that it could also cause mutations if it fits into the genetic code of a human taking the pill. This mechanism of action is specific to molnupiravir; Pfizer’s Covid-19 pill works differently.
The FDA, for its part, dismissed these concerns in documents released Friday ahead of Tuesday’s molnupiravir advisory committee meeting, writing that the “risk of genotoxicity after treatment” with molnupiravir “is low.”
Scientists who initially raised the concerns remain skeptical. In public comments submitted to the advisory committee, Dr. Ronald Swanstrom, professor of biochemistry and biophysics at the University of North Carolina at Chapel Hill, whose lab published an article last spring claiming molnupiravir could cause mutations in mammalian cell cultures, wrote: “Molnupiravir is about to be shipped around the world with a big genotoxic question mark, a point most people who receive the drug will not have the knowledge necessary to fully understand. “
Scientists at Merck have taken issue with Swanstrom’s lab study, although Swanstrom sticks to his lab’s methods.
Key questions for the advisory committee will be what the scope of authorization for molnupiravir should be. The FDA will ask counselors to discuss whether to allow the drug to be used during pregnancy. He will also question the advisers on the risk that the use of molnupiravir could actually create new strains of the virus.
In its own backgrounder, the agency wrote: âIt is still unclear whether the potential for [molnupiravir]-associated changes in SARSCoV-2 spike protein pose a risk to public health, given the intended widespread use of MOV.
Finally, the agency will ask committee members whether the benefits of molnupiravir generally outweigh its risks for adult patients at high risk of severe Covid-19, and what risk factors a patient should qualify.
It’s important to note that the FDA’s briefing materials were written based on initial data from Merck, not updated results announced on Friday that reduce its effectiveness. In an addendum to its backgrounder noting the new data, the FDA noted that the benefit / risk assessments that will be presented on Tuesday may differ from those in the original briefing materials.
Analysts generally expect the drug to receive emergency use authorization, but perhaps for a small population.
“After reading the information documents and taking into account the macro-pandemic situation, we await the authorization of molnupiravir for all patients with one risk factor or moreâ¦ and regardless of the status of previous vaccination / infection” SVB Leerink analyst Daina Graybosch wrote in a note released Monday. .
Graybosch wrote, however, that the discussion will highlight ways in which molnpuiravir appears to be inferior to Pfizer’s Covid-19 pill. âThis includes the risk of harming fetuses and accelerating the rate of viral mutation that can lead to the emergence of new variants of SARS-CoV-2, in addition to relatively lower efficacy,â Graybosch wrote.
FDA advisers are scheduled to meet at 9 a.m. and rise at 5 p.m.
Write to Josh Nathan-Kazis at [email protected]