A new pill to treat people with Covid-19 may be given emergency use authorization by the US Food and Drug Administration before year’s end. The data from a late-stage clinical trial suggest that the drug, molnupiravir, can protect patients who are treated within the first five days of feeling symptoms — lowering their risk of hospitalization and death by half. But who will get them and how will they work? In this Q&A, Max Nisen and Sam Fazeli, who cover health care and the pharmaceutical industry for Bloomberg Opinion and Bloomberg Intelligence, discuss the first Covid-19 oral antivirals.
MN: Who should get this treatment? Anyone who gets Covid, just the unvaccinated, or only people at higher risk of bad outcomes?
SF: The pills will probably be prescribed for the same kinds of people who were studied in the clinical trial: patients who have tested positive for SARS-CoV-2 no more than five days earlier and who have at least one underlying medical condition that raises their risk of severe illness from Covid-19. People at increased risk, according to the Centers for Disease Control and Prevention, include those 65 or older and those who have cancer, chronic kidney or lung disease, diabetes, certain heart conditions or obesity, among other things. That includes so many, it’s easier to say who will probably not have access to molnupiravir: healthy people under 65.
Will the pills be available to those who fit the criteria above and have been fully vaccinated? I suspect they will, because these same patients carry a higher risk of severe disease even if they are vaccinated.
MN: Molnupiravir is supposed to be given within five days of symptom onset. Will doctors need to see the results of a standard PCR test before prescribing it, or will a rapid antigen test suffice?
SF: In the trial, patients were allowed to have rapid antigen tests, and I assume in practice the drug will be authorized for eligible people who test positive using any approved method.
MN: Are other similar pills on the horizon, and are they likely to work as well?
SF: Roche and its partner Atea are working on a Covid-19 antiviral, as is Pfizer, and their clinical-trial data should arrive by the end of the year. The Roche/Atea drug has a mechanism of action that’s similar to molnupiravir’s, but its dosage is smaller. Patients take only two pills every 12 hours for five days, rather than four pills (every 12 hours for five days) for molnupiravir.
Pfizer’s drug works differently. It requires fewer pills, yet it is a combination of two drugs. This means it may be more likely to cause problems for people who are taking other medications (given that the drug it’s combined with can affect the way the body handles other drugs). And this adds a layer of complexity that molnupiravir doesn’t have.
Two other drugs in development — one from Shionogi of Japan and the other from Enanta — work in much the same way Pfizer’s drug does. These are further behind in testing. But neither need the second drug, and that could be a significant advantage.
MN: Are there any particular safety concerns with these pills?
SF: All drugs have some side effects. The question is whether the benefits outweigh or justify the risks. Molnupiravir introduces mutations into the coronavirus genome that make it harder for the virus to replicate. Theoretically, the drug might also cause mutations in any fast-dividing human cells, potentially causing trouble for pregnant women or putting people at risk of cancer. But it is very unlikely that Merck/Ridgeback could have started its large phase 3 trial of molnupiravir without first convincing regulatory authorities that this has not been a problem in a wide range of animal studies. Also, patients’ relatively short exposure to the drug minimizes this risk. To reduce it even more, regulators could limit use of the drug to once or twice a year. No doubt, the regulators will ask Merck/Ridgeback for evidence that they could not have used a lower dose.
MN: For patients who will have a choice, is this treatment preferable to monoclonal antibodies?
SF: This is hard to answer, as no head-to-head trial has been done. Based on the data we have, monoclonal antibodies appear to be more effective. But then, we don’t know how the patients in the molnupiravir trial compare with those in the antibody trials. Monoclonal antibodies are known to be very safe, and to provide relatively lasting protection against the risk of hospitalization. On the other hand, they aren’t as easy to take as ordinary pills. They need to be administered by a health-care professional.
So there is a place for both treatments. And it’s possible that combining the two would provide even better protection. But cost would be an issue. Molnupiravir is priced in the US at about $700 per five-day course. Monoclonal treatment comes to about $2000.
If I were offered a choice and cost were no issue, I’d take the monoclonals.
MN: Might the Covid virus develop resistance to molnupiravir, much as bacteria develop resistance to antibiotics?
SF: Probably not. It’s a theoretical possibility, but I think Merck/Ridgeback will have data looking at emergence of resistance. Molnupiravir’s target is an aspect of the coronavirus that is relatively highly conserved — that is, the virus may not be able to mutate in a way that would avoid molnupiravir’s effect.
MN: How will the pills affect sales of Covid-19 vaccines? Investors seem to think sales will fall, but vaccines are still the most effective option, right?
SF: Unfortunately, if the drug is authorized broadly and not limited to at-risk patients, it may lead some vaccine-hesitant people to opt for molnupiravir instead. Even if it is approved only for higher-risk individuals, some of them may still prefer to take the drug. This would be misguided, because vaccines provide much greater protection against hospitalization — as much as 90% protection, according to Pfizer-BioNTech’s latest vaccine data.
MN: Will the pill make people hesitate to get booster shots, since they offer less relative benefit?
SF: That’s a very good question. We don’t know what level of benefit boosters provide, but consider this scenario: It’s possible that after delta has run its course, the variants that are capable of escaping immunity (gained either through a prior infection or vaccination) may start to make a comeback. Indeed, very recent data show that antibodies from people who were infected by the delta variant are almost unable to neutralize the beta variant. Giving a third of shot of the vaccine — which I view not as a booster but part of the primary vaccination schedule — raises the antibody level high enough to neutralize all the key known variants. Such a high level of immunity is very likely to reduce the risk of viral transmission. We have no data on viral load or risk of transmission from people treated with molnupiravir. Vaccination is a much more lasting strategy than drug therapy.
MN: What’s the treatment going to cost, and who’s going to pay?
SF: The five-day course of 40 pills was priced at $700, based on the US government contract signed in June 2021. The price will probably be the same for most affluent countries. For developing nations, Merck has licensed the drug to several generic manufacturers. The companies will probably still try to make some profit, though this is not clear.
As to who pays, I think in the US and most other countries, at least during the pandemic, it will be government. For most patients, the pills should be free.
Bloomberg
