Molnupiravir, an antiviral pill manufactured by the pharmaceutical company Merck in partnership with Ridgeback Biotherapeutics, showed promise in a Phase III clinical trial late last week. If approved by the FDA and other global regulators, it will offer an easier way to treat people who have been infected with COVID, but not yet hospitalized. That could save lives and reduce the burden on tattered ICU wards—but because the drug is a treatment, not a preventative, it can only blunt the pandemic, not slow it down entirely.
The study consisted of 775 recently diagnosed COVID patients, all of whom were at risk of severe disease. Patients took two pills a day for four days, and then were monitored for about the following month.
Among those patients, the drug appears to have dramatically reduced the incidence of severe disease, according to a Merck press release. Patients who received the real drug were half as likely to be hospitalized as those who got a placebo: 14.1 percent vs 7.3 percent. And eight patients who received the placebo died, while no one who received molnupiravir did.
The effect was so clear, the drug company says, that an independent panel of experts recommended shutting down the trial and seeking regulatory approval.
Developing treatments for viruses is much more challenging than creating antibiotics to fight bacteria, in large part because viruses outsource most of their reproductive functions to the host themselves. Other approaches to treating COVID, like convalescent plasma therapy or ivermectin, have ended up falling flat.
According to Richard Plemper, who studies antivirals at Georgia State University, the molecule that underlies molnupiravir has been investigated as a treatment for influenza for more than five years. When the pandemic unfurled, his team, which had demonstrated the compound’s efficacy against influenza in ferrets, pivoted to SARS-CoV-2.
He says that the drug acts as a substitute for one of the molecules that make up RNA. As the virus replicates, it will incorporate bits of molnupiravir into its genetic code. But when it tries to replicate again, the drug scrambles the code slightly. “We introduce random mutations into the viral genome, and that is very quickly catastrophic for the virus,” says Plemper. “You don’t need hundreds or thousands of mutations for the viral population to mutate itself to death.”
There are caveats, some of which we’ve seen before. Although Merck says it plans to seek FDA emergency use authorization “as soon as possible,” it hasn’t actually released full trial data yet, which means that we’re relying on a press release. That’s been a consistent sequence from drug companies announcing vaccine trial findings, which makes it hard to weigh the results at the time they’re announced.
If the drug is approved, it will be used in the limited window after someone is infected, but before they progress into severe illness. As Science reported this spring, Merck had been doing tests on molnupiravir in hospitalized patients, but discontinued the trial after disappointing results.
Patients who received molnupiravir in the trial had shown COVID symptoms within five days of starting treatments. It’s likely that FDA approval would be for people who are similarly recently infected—meaning that doctors would have to diagnose COVID early in order to treat it.
“It really is going to put the onus on us to make sure we’re going to test people quickly,” Annie Luetkemeyer, a professor of medicine at UC San Francisco told NPR over the weekend. “And if they’re positive and symptomatic, that we treat them quickly.”
But Plemper thinks that’s attainable. “With contact tracing, and the enormous expanse in diagnostic infrastructure that we’ve made throughout the pandemic, we can identify patients before they develop clinical signs… I very much hope that that improves the health status of many.”
That places it in roughly the same category as monoclonal antibody therapy, a treatment approved last fall to treat people who have been experiencing symptoms for a maximum of ten days. Like molnupiravir, monoclonal antibodies reduce a person’s viral load, and decrease their risk of hospitalization.
But the antibody therapy is expensive—a round of treatment costs more than $2,000—and have to be delivered with an injection. The federal government has picked up the bill for the drug itself, but patients may still need to pay for the administration. Some states have set up their own monoclonal antibody distribution centers to get around that problem, but it introduces a substantial barrier to treatment, unlike a take-at-home pill.
“The key factor is that [molnupiravir is] orally bioavailable,” says Plemper. “We do not need IV administration. We can reach outpatients.”
But like monoclonal antibodies, molnupiravir is for the moment expensive, and capacity may be limited. The U.S. government has agreed to buy 1.7 million rounds of treatment at $700 apiece—more than a billion dollars total. Meanwhile, the CDC estimates that more than 40 million Americans have caught COVID over the last year and a half. This winter’s delta wave could end up running through those supplies quickly.
And while many insurance networks have agreed to pick up the full cost of COVID treatment, that’s changing. According to research published by the Peterson-KFF Health System Tracker in August, the majority of large insurance companies in each state are beginning to charge for COVID hospitalization. Soon, getting the prescription for COVID drugs could end up being more expensive. And outside wealthy countries, molnupiravir is likely to be even less accessible, although Merck said in its press release that it has deals with generic drug manufacturers to ramp up production “to accelerate the availability of molnupiravir in more than 100 low-and-middle-income countries.” Whether it will reduce the price in those countries remains to be seen.
For an individual staring down a positive test, a drug like molnupiravir will be a relief in a year with few of those. But for the country and the world, the way out is still through vaccines—they cost between $5 and $20 per dose, and stop most people from catching COVID in the first place, or at least from getting a severe case. “The best thing to do is to vaccinate, and to vaccinate as many people as possible,” says Plemper. “But we have seen with the emergence of diverse variants of concern, that it’s not guaranteed to silence the pandemic. We need vaccination, and we need effective therapeutics. I think that’s our best prospect of leaving this thing behind.”
Correction 10/6/21: This article has been updated to reflect the fact that molnupiravir is developed in partnership with Ridgeback Biotherapeutics.