New Pill Is a Potential Game-Changer in the COVID Battle, CU Anschutz Expert Says

What is your initial reaction to the development of molnupiravir as a treatment against COVID?

I think this drug is very exciting, and then there are two others (antiviral oral pills being developed by Pfizer and Atea Pharmaceuticals-Roche, respectively) that are not far behind, so we need to see if those other two work. But this just makes treatments so much easier for everybody – clinicians, patients – because all we have now are infusions. This opens the door for ambulatory treatment (of COVID-19).

What did you think of its efficacy in the clinical trial?

I thought it was really quite exciting. They stopped the trial early because there was overwhelming evidence that it worked. I think it’s very encouraging.

Do you think oral pills will become a new trend in the treatment of SARS-CoV-2?

Yes. Vaccination definitely is the umbrella over everything. But if we can treat COVID with these oral medications, I think it changes the efficiency of care altogether. And I think that’s the way we’ll head. We’ve got antibodies, but you have to be hospitalized or go into a clinic for an infusion.

In the HIV world, where I came from, I can see the parallels for treatment. With COVID, it started with one drug: remdesivir, the very first one administered in the hospital to very sick patients. By itself, it didn’t have that great of an effect, much like AZT (the first HIV drug). And then with the subsequent drugs, it’s incumbent that they improve. Additionally, for HIV, we learned the advantages of combination therapy. It’s synergistic when you use a combination of drugs that work on different parts of the virus. It might be where we land one day (in the fight against COVID).

How does molnupiravir work against SARS-CoV-2?

The virus has to replicate its genetic material – that’s a key for all viruses. So, this drug causes the virus’s genetic material to incorporate genetic errors. The virus becomes non-viable because there are so many errors built up. In HIV, this same class of drugs (nucleoside analogs) causes the genetic chain to stop. (Molnupiravir) is a little different, but it’s a direct-acting antiviral, so it works right on the virus, not on the immune system like some of the other (COVID) drugs you hear about.

And it’s shown to be effective against SARS-CoV-2 variants, including delta and gamma?

Yes, so far it works against the variants.

What about Merck’s ability to produce enough of the medicine? Is there an ability to make large quantities of the drug?

Yes, I think that’s another really advantageous feature. As I understand, it’s actually pretty easy to synthesize – to perform the chemical process – so unlike remdesivir, which has a lot of steps that go into the final product, this one is just a few steps. So, it should be easy to manufacture in bulk. Merck said in a press release they expect to have 10 million doses ready by the end of the year. It shows pretty good scale-up.

Are there any potential side effects or potential warning signs about the drug?

Because of how the drug works, you want to be sure you don’t introduce errors in the genetic material of our (healthy) cells, and Merck has done some studies and demonstrated that there is no evidence of that. You do the animal studies before you go into human (trials), and the animal studies also look good.

You also want to get longer-term safety information. They’ll have to do things like ensure that it is safe in people who want to become pregnant – both men and women (enrollees in the recently published trial were instructed to abstain from sex or use contraception). I think there is a little more work to be done to dot your I’s and cross your T’s with the safety studies, but so far, in the human studies, it looks safe.

A few countries – Australia, Singapore, Malaysia and South Korea – already have agreements to buy molnupiravir doses even though, at least with the FDA in the United States, regulatory hurdles haven’t been fully cleared. Does that surprise you that some countries are going ahead with ordering supplies?

I think COVID has changed things a little in that regard. The vaccines, the antibodies, etc., were all relatively fast. I do think some of our practices have sped up a little bit, but we are still using due diligence for reviewing safety and efficacy. With the countries that are moving fast, I’m sure they’ve got their experts looking at (the drug) and doing their best (to analyze its safety and effectiveness).

What do you think about the wave of misinformation that has convinced many people that they know more about how to treat COVID-19 than the medical establishment and experts, such as the push for use of ivermectin?

It goes to trusting experts again. Ivermectin is a replay of hydroxychloroquine. The exact same thing happened. I understand the confusion in the public because there are studies that were done – but they were done poorly, and not well peer-reviewed. These make it into the literature, and people point to them, but some have ended up being retracted because scientists found flaws (in the research). And so now there’s all this confusion. But the experts that we talk about, they sift through all of the data from all the studies. They found significant errors in the ivermectin studies people point to. So, we have to rely on these experts. These are the best of the best in our field who are reviewing these studies and the recommendation is not to use ivermectin for COVID-19.

Would you describe molnupiravir as a possible game-changer in the fight against COVID?

I think so; I was impressed with the results. You can’t question the result, and they stopped the (most recent) trial early. I think what we’ll see in the future is molnupiravir will become part of a cocktail way that we treat COVID patients. I think this is a very exciting development; it clearly works in the population they studied.

It’s exciting, too, that they’ve got other studies going with prevention, using molnupiravir to possibly prevent COVID. I think that could be really important as well. I think molnupiravir brightens the future of managing COVID.