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The announcement that a pill from Merck and partner Ridgeback Biotherapeutics kept Covid patients out of the hospital made headlines and moved stocks late last week. But as is so often true when data are released by press release, there are still many questions left unanswered.

Doctors are excited about the medicine, molnupiravir, because a regimen of pills, even one that involves taking several pills twice a day for five days, should be far easier to deliver to patients than current antiviral Covid-19 treatments, which must be given intravenously. But it’s still unclear how widely this treatment will be used. There will also be debate among financial analysts at investment banks regarding exactly how many billions of dollars in sales the new drug will generate.

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Here are some things to keep in mind as we learn more about molnupiravir and about other Covid-fighting pills in development at other companies.

How many other anti-Covid pills will end up proving effective?

One of the reasons that the success of molnupiravir is such a big deal is that there were questions as to whether an antiviral pill could help Covid-19 patients if given early enough. This medicine certainly did, reducing hospitalizations by 50%; it also appeared to have an impact on whether patients survived. That makes it a game-changer. Its success also ups the odds that other medicines will prove effective, too.

Results for other drugs are likely to be released by the end of the year. That includes data about a similar pill, also given as a five-day course, from Atea Pharmaceuticals and Roche, and about a pill developed by Pfizer that is from a different drug class and might be combined with molnupiravir.

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Another positive note for all these drugs: remdesivir, the intravenous antiviral made by Gilead Sciences, also showed positive results when used for three days after onset of symptoms. That’s not practical — it had to be given via IV for three days — but bodes well for antiviral pills showing some efficacy. It’s even possible those pills might be combined.

How safe is molnupiravir?

Obviously, a drug given early in Covid needs a clean safety profile. So far, the data included in the press release look very good. Patients in the placebo arm were three times more likely to withdraw from the study due to apparent side effects than those who actually received molnupiravir. That likely means the side effects of Covid were worse than those of the drug.

But only so much can be seen from that kind of data. Molnupiravir works by messing up the way the virus copies RNA, its genetic material, preventing viral replication. There is some concern it could be mutagenic, meaning that it could cause mutations. One result could be that it causes birth defects. In the clinical trial, both women and men were told to either abstain from sexual intercourse or to use contraception while they were taking the drug and for at least four days after. Women of childbearing age also needed a negative pregnancy test to start taking the medicine.

Could there be other effects? In a conference call with reporters Friday, Daria Hazuda, a top Merck virologist, said that Merck and Ridgeback had studied the mutagenic potential of the drug in both cell lines and in animal models that are routinely used in drug development and which are accepted by regulatory agencies.

“I would say that in all of the models where we have looked, we have seen no evidence of the potential for mutagenicity for this agent,” Hazuda said. “We’re very comfortable that the drug will be safe if used as intended and at the concentrations where we have looked and in the concentrations which we are achieving in patients.”

Will molnupiravir be used only in unvaccinated patients?

Merck’s trial was conducted entirely in patients who had not been vaccinated. That made it much easier to show that the medicine can reduce hospitalization and death — because patients who have not previously been vaccinated are more likely to be hospitalized or die.

But does that mean that, in practice, the drug will only be used in unvaccinated patients, or will it be used in cases of breakthrough infections? It’s hard to say. Patients with breakthrough infections are at lower risk of hospitalization, which could change the risk-benefit calculus around the medicine.

So how big will the market be?

Daina Graybosch, an analyst at SVB Leerink, forecast in a note to investors on Monday morning that molnupiravir sales will peak near $5 billion a year in 2022.

Built into this are a number of assumptions, among them that the first-mover advantage will mean that Merck and Ridgeback will be used more than the other pills in development and that vaccinated patients with breakthrough infections will be eligible to receive the drug, too.

Timothy Anderson of Wolfe Research, a standalone equities research firm, takes the other side, essentially saying it is too soon to put a number on molnupiravir sales, in part because data from competing firms are not available but also because other questions remain.

“Vaccination rates continue to rise in the US and other developed markets, meaning the cohort of patients who would qualify for molnupiravir (i.e. mostly those who are unvaccinated, at higher risk) will shrink over time,” Anderson wrote in a note to clients.

Successfully using the drug, he pointed out, will also require that patients get tested early in their disease course. If people start to skip getting tested, they won’t receive molnupiravir.

What will it cost and who will pay?

Most analysts are basing the cost of molnupiravir on the $1.2 billion the U.S. government spent to lock up 1.7 million courses of the medicine, which works out to $700 per five day course. But Anderson points out that the cost for a new pill to treat influenza developed by Roche is just $150 per course. Will the $700 price hold up?

Questions about payment and distribution could play a big role in how big the market for molnupiravir gets. Anderson assumes in his note to clients that, in the U.S., insurance companies will be paying for the drug through traditional channels. He expects that at $700, insurers will restrict use of the drug to those who are unvaccinated and have multiple risk factors for disease — basically similar profiles to those who are in the trials.

But it’s also possible that sales in the U.S. might be mostly to the government. This is how things have worked with both remdesivir, used in hospitalized patients, and the monoclonal antibodies developed by Regeneron and Eli Lilly. Will the government handle the distribution of a pill granted an emergency use authorization in the same way that it has handled the monoclonals?

How will the availability of Covid pills affect vaccines and other treatments?

It doesn’t make any sense to forego a Covid vaccine because a pill to treat the disease exists. The benefits are additive, and someone who got a breakthrough infection and then the pill has a much lower risk of hospitalization than someone who just relied on the pill.

But it seems likely that some people will feel less urgency to get vaccinated as a result of molnupiravir’s existence, and shares in Pfizer, BioNTech, and Moderna all fell on Friday. The latter two are down again Monday morning.

Shares in Regeneron also fell, as oral drugs create uncertainty for its monoclonal antibody treatment for Covid. The landscape there is uncertain, with other companies coming forward with antibodies that may have advantages. One small firm, Adagio Therapeutics, recently presented early data on an antibody it thinks could be given as a single shot.

How does this treatment relate to ivermectin?

This is simple: it doesn’t. But it’s worth taking a look at what data are available for each.

Ivermectin, ironically, is another Merck drug. The company’s donation of the medicine to be used to combat a parasitic disease called river blindness is one of the great examples of pharmaceutical philanthropy. It’s also used as a veterinary drug to treat heartworm.

Early in the pandemic, there were studies in cell cultures that showed that ivermectin and another drug, hydroxychloroquine, might be worth testing as Covid-19 treatments. Multiple studies have failed to show a benefit for hydroxychloroquine, but the picture is murkier for ivermectin. Still, one of the largest studies showing a benefit was withdrawn due to widespread flaws.

There is a study conducted in Brazil, the Together Trial, that tested a three-day course of ivermectin compared to placebo and showed there was no benefit on hospitalizations and ER visits. That would make it unlikely that ivermectin, an old antiparasitic, would have efficacy approaching this newer antiviral.

Drug companies are unlikely to conduct large, rigorous studies of older generic medicines — although Novartis did begin, then stop, a hydroxychloroquine study. But right now it is unlikely that ivermectin is the oral Covid medicine the world needs. Molnupiravir, on the other hand, might be.

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