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Andy Larsen: Explaining molnupiravir, a new COVID drug with surprisingly effective test results

Molnupiravir will likely get emergency approval in coming weeks, and could signal a step forward for medicine against other viruses.

(Georgia Kirkos/McMaster University via AP)

It’s always nice to get some unexpected good news.

That’s especially true in COVID World, where the situation (Full hospitals! Thousands of deaths! Protests, stupidity and denial!) always seems helpless.

But thanks to some out-of-the-blue good study findings last week on a drug called molnupiravir, we have another promising tool in our fight to keep sick people from dying from COVID-19 — and hopefully, as a result, another step towards semi-normalcy.

But what is molnupiravir? Let’s dig into the background on this drug, what it does, and why people are excited about it. An important shoutout here should go to Science Magazine’s Derek Lowe, whose In The Pipeline blog has been covering the molnupiravir story throughout the year.

History and how it works

Atlanta-based Emory University owns a spinoff nonprofit called Drug Innovation Ventures, a lab which works to create new drugs. In particular, they’ve been looking into antiviral drugs, which are notoriously difficult to make — if they were easy, the coronavirus pandemic wouldn’t have been such a big deal!

But researchers had a good idea: What if you were able to make a chemical compound that messes with the way viruses copy themselves? In order for it to work, though, you’d have to interrupt the process of viral replication within someone without interfering with the surrounding human body’s normal processes of copying its own cells. Sounds tricky.

Good news, though: Viruses and cells don’t replicate themselves in quite the same way. Human genetic material comes in the form of DNA, while virus genetic material is RNA. In particular, viruses make copies with a tool called RNA-dependent RNA polymerase (RdRp), which isn’t used by normal human cells. If you could ruin that tool, you could significantly slow down the ability of viruses to copy themselves, grow inside of you, and make you sick.

Getting that chemical compound exactly right has been challenging, though: You need it to bind to the RdRp, but not to anything else. So over the last decade or so, scientists have been trying different formulas of “polymerase inhibitor” drugs. Remdesivir, for example, is one such formula.

And so is molnupiravir. The formula was named after Thor’s Hammer — called Mjollnir — from Norse mythology, after researchers found this compound worked really well in petri-dish testing. As the Encyclopedia Brittanica writes, Thor’s hammer Mjollnir was “the symbol of his power. Forged by dwarfs, the hammer never failed Thor; he used it as a weapon to crash down on the heads of giants.”

This Thor’s Hammer, though, comes in an unassuming guise: Unlike remdesivir, which is delivered by IV, molnupiravir can be taken in pill form.

Before the pandemic, researchers were getting ready to run trials for molnupiravir against the flu. But with the interest and money thrown into the development of coronavirus drugs, Emory’s team contracted with Ridgeback Biotherapeutics, who then worked with Merck, the pharmaceutical giant, to try to get the drug produced and tested more quickly. Just like with vaccines, new drugs require three phases of testing with increasingly large sample sizes to go well before a drug is approved by the Food and Drug Administration.

Testing

Preliminary results from Phase III testing were announced Friday — and indeed, results were so good that they stopped the trial early, so they could give molnupiravir to the placebo group too, and potentially save their lives.

Here’s how the experiment was designed: Merck found 762 unvaccinated people who were within five days of a diagnosis with coronavirus who had at least one significant risk factor: either they were obese, 60+, diabetic, had heart disease, or a combination of the above. They then split them into two nearly equally sized groups: 377 who got a placebo and the typical coronavirus standard of care, and 385 who took the molnupiravir pill.

In the placebo group, 14.1% of the patients were hospitalized. In the molnupiravir group, only 7.3% were. In the end, eight people ended up dying in the placebo group. Zero molnupiravir takers died.

What about safety? Well, there were more adverse events in the placebo group than in the molnupiravir group. Funnily enough, those in the placebo group were actually three times more likely to withdraw from the study, citing side effects of the pill they were taking. They were actually receiving those side effects from COVID-19, not the sugar pill.

These are the most effective results we’ve seen in a reasonably cost-effective therapy so far.

Because of these results, the independent monitoring group looking at the data decided to halt the study early — probably saving the lives of some in the placebo group, but hurting the sample size of the test.

What comes next

Still, if the FDA likes the results when they thoroughly analyze them, and they’re expected to, molnupiravir will likely get an Emergency Use Authorization and be added to normal care for the coronavirus in the coming weeks.

Because molnupiravir is a pill, it’s cheaper to produce and give out than remdesivir or monoclonal antibodies. In the summer, Merck signed a deal with the U.S. government to supply 1.7 million courses of molnupiravir for $1.2 billion, which works out to be $700 a course. Each course lasts for five days.

That’s among the cheapest coronavirus therapies available, but still a price likely too expensive to give the drug to people as a COVID-19 preventative, even for those at extremely high risk. A separate trial to use the drug in that way is currently ongoing. Meanwhile, Merck says it’s working with generic manufacturers to supply lower-income countries with the pill; that may also push the price down to something more reasonable.

You’ll note that the trials happened wholly in the unvaccinated, and of course, those are the people most likely to die from the coronavirus right now. But molnupiravir also could save vaccinated lives: For those whose vaccine was ineffective, especially due to immune system weakness, molnupiravir’s very different mode of operation could be a lifeline.

Some are worried that the availability of a pill to better treat the virus will reduce vaccinations. Honestly, for people to reject a vaccine that’s 90% effective in preventing hospitalization in favor of a 50% effective pill seems insane to me, but, well, a lot of insane things have happened in the last year and change. And in the end, we shouldn’t stop scientifically progressing because of the existence of tinfoil hat wearers, no matter how frequently we see malleable metal reflecting the sun off people’s heads.

Besides, molnupiravir’s ability to make a dent against the coronavirus could well be the harbinger of its effectiveness against other viruses — the flu, hepatitis, and so on. If we’re able save those lives too, even better. We could, possibly, even use molnupiravir against viruses we haven’t encountered yet, in case another pandemic should arrive.

If you’re looking for a silver lining to all this bad news, this is it: We’ve made significant scientific advances in a hurry, which should make our lives healthier in the coming years and decades than they would have been otherwise.

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