On Friday morning, pharmaceutical firm Merck issued a statement saying that, in consultation with the U.S. Food and Drug Administration (FDA), it has stopped recruiting patients to test its antiviral drug molnupiravir for the prevention of COVID-19. It’s not stopping because of problems. It’s stopping because the testing results so far have been so promising that Merck intends to make an immediate application for an Emergency Use Authorization.
Molnupiravir is one of several antiviral drugs under evaluation either for preventing COVID-19 or for treating those who had tested positive. The drug was nearing the end of Phase 3 enrollment, with Merck reporting that the 1,550 patient sample size represented 90% of their initial goal. However, when looking at intermediate data, the results were so positive that it seemed appropriate to suspend recruitment and move immediately to make the treatment available through the FDA.
Looking at interim data, molnupiravir reportedly “reduced the risk of hospitalization or death by approximately 50%.” That might be an undersell. While 7.3% of patients who received molnupiravir were hospitalized within a month of contracting COVID-19 compared to 14.1% of those who received a placebo, death rates differed significantly. According to the statement:
Through Day 29, no deaths were reported in patients who received molnupiravir, as compared to 8 deaths in patients who received placebo.
A 50% reduction in hospitalizations. A 100% reduction in deaths. Though this is a small sample group, those are the kinds of numbers that make getting this treatment out to the public as soon as possible worth taking extraordinary steps. And since Merck already made a deal to provide enough for 1.7 million people back in June, the new treatment could be available as soon as it’s approved.
In the case of molnupiravir, patients who had tested positive for COVID-19 take four pills twice a day for five days.
Molnupiravir is available as a pill, is relatively easy to manufacture, and can be taken at home by the patient. These are significant advantages over monoclonal antibody treatments that have to be administered through an IV by medical personnel, are expensive, and are available in limited quantities.
Antiviral medications take three broad approaches: block receptors to prevent viruses from binding to human cells, interfere with the virus's ability to replicate within a cell, or boost the immune system's ability to fight off infection. Researchers have found success against a variety of viruses—including HIV—using all three approaches.
Molnupiravir falls into the “interfere with replication” approach. Rather than targeting the spike protein that the SARS-CoV-2 uses to attach to human cells (the approach taken by all current vaccines and some other treatments in trial), molnupiravir targets the enzyme RNA-polymerase, which the virus requires to make copies of itself. By inserting a “mistake” into the enzyme, molnupiravir prevents replication.
At first glance, molnupiravir appears to be exactly the kind of treatment that everyone might hope for, but the efficacy of some antivirals has recently been called into doubt. According to manufacturer Genentech, the commonly administered antiviral Tamiflu (oseltamivir) reduces the chance of serious flu symptoms by 44% and cuts the hospitalization rate by 63%. The CDC and FDA also recommend the treatment. However, some researchers suggest that the benefit of Tamiflu for most patients is small, and there have been concerns raised about its risk/benefit ratio.
Adding to potential concerns about molnupiravir is that everything currently being heard is coming straight from the manufacturer. To date, Merck has not released the raw data from its Phase 2/3 trials, and there has been no journal publication or peer-review of the information featured in their announcement.
But there’s one odd reason to be hopeful about molnupiravir—it’s old. The antiviral began development as a treatment against the viruses responsible for SARS and MERS. It was first intended as a prophylactic, or preventative, medication at a point when there was concern that either of these viruses could spark an epidemic. Initial tests were hopeful, which is why the drug was revisited for COVID-19 treatment testing.
This isn’t a drug that came out of left field being used for something far outside its original scope. This is an antiviral medication specifically designed to target viruses that are very closely related to the one that causes COVID-19. The available information looks promising.
It’s still no substitution for vaccination, even if everything Merck reported turns out to be true. But it does appear to be a significant advancement in COVID-19 treatment. Molnupiravir could treat those who test positive. The fact that molnupiravir is a home-administered pill opens the possibility that it could be used as a preventative for those exposed even before testing positive.
In June, early indications led to Merck reaching an agreement with the government to provide enough molnupiravir for 1.7 million “courses.” In July, the company announced that an “open-label” clinical trial in India had generated enough positive results that its partner in that country would seek approval from the Drug Controller General of India (DCGI).
If this holds up, it’s a big deal. A big good deal. We need more of those.