The Food and Drug Administration may soon authorize the first pill to treat Covid-19 after the pharmaceutical giant Merck reported strong results from its antiviral drug molnupiravir earlier this month. On Monday, Merck filed for an emergency use authorization from the FDA, which would allow doctors to begin prescribing the drug. Based on the approval timeline for past Covid-19 drugs, the FDA could make a decision within days or weeks.
Clinical trials showed that the drug reduced the risk of hospitalization and death in at-risk patients by 50 percent, according to the company’s interim analysis.
“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” said Robert M. Davis, CEO and president of Merck, in a statement.
A new and effective Covid-19 treatment — if approved by health regulators — could be a versatile tool for doctors to treat Covid-19 patients and could ultimately save lives. While there are a number of treatments for Covid-19 on the market, many of them are expensive, difficult to administer, not widely available, or only marginally effective. Meanwhile, treatments that have little evidence behind them, like the antiparasitic drug ivermectin and the anti-malaria drug hydroxychloroquine, have gained traction in some circles.
Molnupiravir, originally developed to treat influenza, could solve many of these challenges. It’s administered as a twice-a-day batch of four pills for five days, compared to other Covid-19 treatments that require expensive intravenous transfusions, such as monoclonal antibodies and convalescent plasma. The antiviral drug remdesivir, currently the only drug with full Food and Drug Administration approval to treat Covid-19, also has to be delivered into the bloodstream.
A drug like molnupiravir (the name is a reference to Thor’s hammer, Mjölnir) could also help compensate for persistent gaps in Covid-19 vaccination coverage, both in the United States and abroad.
However, the results were announced in a company press release, which carries less scientific weight than a peer-reviewed paper or even a pre-print article that lays out the data for outside scientists to examine. Merck’s findings did come from a randomized phase 3 clinical trial of 775 adult Covid-19 patients. The participants had mild to moderate disease and were deemed to be at-risk but not hospitalized when the trial began in early August.
By day 29 of the trial, 7.3 percent of patients who received molnupiravir had died or were hospitalized, compared to 14.1 percent of patients who were in the placebo group (meaning they did not receive the drug). Merck says molnupiravir was also effective against coronavirus variants, including gamma, delta, and mu. The trial was halted, with the approval of regulators, once these results showed the drug’s effectiveness.
A group of independent experts saw the data and said "we've seen enough"— Ashish K. Jha, MD, MPH (@ashishkjha) October 1, 2021
And stopped the trial because the drug was clearly working
That's important verification
It also makes me far more optimistic about other similar therapies being studies for COVID will pan out
“With these compelling results, we are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic and will add to Merck’s unique legacy of bringing forward breakthroughs in infectious diseases when they are needed most,” said Davis.
The federal government is already planning for its potential approval: It has committed to buying 1.7 million courses of molnupiravir treatments for $1.2 billion (about $700 per course), and production of the drug has already begun. Ridgeback Biotherapeutics and Merck expect to make 10 million courses of the drug by the end of the year.
It could still be weeks or months before most people will have access to the little brown pill. And even when it is available, there may still be holdouts resistant to getting treated for the disease.
How Merck’s new antiviral drug molnupiravir works
Viruses are tricky beasts to corner. They are passive parasites and can’t reproduce without hijacking the machinery of a host cell. That makes it really difficult to come up with a drug that can interfere with a virus’s life cycle without also causing collateral damage to healthy human cells. And because viruses mutate so quickly, an effective treatment can become less so over time.
Compare that to bacteria, which contain all the biological hardware they need to make copies of themselves. Their machinery is different enough from human cells that the class of drugs known as antibiotics can kill off many bacteria with minimal damage to humans.
Molnupiravir works a lot like the antiviral drug remdesivir (-vir is a suffix commonly used for antiviral drugs). The SARS-CoV-2 virus, which causes Covid-19, makes copies of itself by encoding instructions on RNA, which is made up of “base” molecules identified by the letters A, C, U, and G. While remdesivir imitates A (adenosine), molnupiravir can mimic U (uracil) or C (cytosine).
When the virus incorporates remdesivir into its RNA, the drug causes its reproductive cycle to stall. Molnupiravir works a little differently, causing genetic mutations that hamper the virus.
Crucially, these drugs can fool the virus, but they don’t fool human cells, so they have a targeted effect and for the most part leave the human cells alone.
Merck didn’t note any specific side effects from molnupiravir in its press release and said the rate of complications was similar between the placebo group and the treatment group in the clinical trial. Unspecified side effects occurred in 35 percent of molnupiravir recipients but occurred in 40 percent of the placebo group.
Molnupiravir faced some of controversy in earlier stages of development. Several researchers previously raised concerns that molnupiravir’s mechanism could lead to some unanticipated problems. Rick Bright, the former head of the Biomedical Advanced Research and Development Authority, alleged in a whistleblower complaint last year that his agency was pressured into funding the manufacture of the drug (then known as EIDD-2801) before they received adequate safety data. The FDA tends to pay close attention to safety concerns as it evaluates drugs for emergency use.
3/5 one concern that it introduces virus mutations or potential mutagenic probably means it won’t be recommended in pregnancy. I seem to remember my good colleague @RickABright had a concern about this drug when he was at BARDA so maybe he can comment. Also important to remember— Prof Peter Hotez MD PhD (@PeterHotez) October 1, 2021
Molnupiravir fills in a crucial gap in the response to Covid-19
While the US has multiple highly effective vaccines that help our immune systems fight Covid-19, the vaccination rate has slowed and many holdouts remain. At the same time, many other countries still don’t have access to enough vaccines. The unvaccinated continue to make up the majority of hospitalizations and deaths, with fatalities currently around 2,000 per day in the US alone.
Treatments for Covid-19, therefore, remain a vital component of the response to the pandemic. But developing new drugs to treat an illness is expensive and time-consuming, which is why researchers have been eager to find off-the-shelf therapies that have already been deemed safe to use against other ailments. Some have proven fruitful, like the corticosteroid dexamethasone. Scientists have also seen promise in the antidepressant drug fluvoxamine as a therapy.
New drugs like molnupiravir require more testing and review, but they offer the possibility of a stronger, more targeted approach. A drug like molnupiravir could be especially useful because it is administered in the early stages of the disease. Since it’s just a pill, it may spare the patient a trip to a clinic for a transfusion for treatments like monoclonal antibodies. That reduces the chances of an infected patient transmitting the virus to medical staff, and it averts potential complications associated with transfusions.
And while $700 for a course of molnupiravir isn’t exactly cheap, a transfusion setup alone can cost $1,000, and that’s on top of the cost of the drugs delivered intravenously. A course of monoclonal antibodies can cost $2,100, while remdesivir can cost $3,100.
Pills are also much easier to store and transport than transfused drugs, so they can reach more remote areas with fewer resources.
That’s why some of the biggest effects of molnupiravir could occur in other countries, particularly in places where Covid-19 vaccines have yet to gain much of a foothold. Merck said it is setting up tiered pricing for molnupiravir, meaning that it could cost less in other countries, and is licensing its production to five generic drug manufacturers in India to build up its supplies.
Treatments do help people get better — but it’s important to remember that vaccination remains the most effective tactic for controlling the pandemic. Vaccination can prevent sickness in the first place, and even the most expensive vaccines are dirt cheap compared to most therapies for the disease. The initial two doses of the Pfizer/BioNTech vaccine and the Moderna vaccine cost about $50.
Other measures beyond drugs remain critical too. Wearing masks, social distancing, and testing for Covid-19 are still effective, and the arrival of an effective drug won’t be a reason to let our guard down. The existing pillars of pandemic response will remain crucial to keeping this deadly disease in check.