Covid pills are ‘very promising’ – but what are the challenges in using them?

Andrew Pekosz, professor of microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, described the pills as “very promising”.

“There is an important role for these in terms of limiting severe disease,” Pekosz said “It’s just going to be a challenge to use them effectively.”

Those challenges include the fact that supplies of the Pfizer treatment are very limited, while the Merck treatment is less effective than hoped. And the pills aren’t for everyone.

Both treatments will only be given to people at high risk of being hospitalized or dying from Covid-19, which were the populations studied in the clinical trials. The Merck treatment will not be given to children or pregnant people. Pfizer’s pills aren’t recommended for those with liver or kidney issues, and it may cause other medications to work differently during the treatment course.

There’s also the issue of access. The pills must be taken as soon as possible after a positive test – and tests can be difficult to find in some of the hardest-hit places, with results often taking days to return. The treatments are also only available by prescription from a doctor or health worker, limiting those who can get hold of it.

And only 65,000 courses of the more effective Pfizer treatment will become available this month, with another 200,000 courses arriving in January amid an anticipated surge of hundreds of thousands of cases as the Omicron variant spreads. Washington DC, for instance, will only receive enough for 120 people despite having the highest rate of new cases in the country.

“It’s going to be very, very limited in terms of being able to find it,” Pekosz said.

And those shortages are likely to persist in the short term. The antivirals are complex to create and it will take six to eight months to ramp up production, with Pfizer expecting to make 120m courses of the treatment in 2022.

The US government pre-ordered 10m courses of Pfizer’s treatment and 3m n of Merck’s. Like the vaccines and monoclonal antibodies, government-purchased antivirals will be given for free.

Beyond supply, another challenge of Paxlovid will be drug-to-drug interactions. Not all medications are affected, but certain ones – some heart medications and blood thinners, for example, as well as herbal supplements like St John’s wort – could be affected by the treatment. Those who receive the Pfizer medication will need to work closely with their doctors to monitor these medication interactions.

The Merck treatment will be more widely available at first, but it only reduced hospitalization by 30% among high-risk patients.

“That was not a magic pill for sure,” said Peter Anderson, a professor of pharmaceutical sciences at the University of Colorado.

The Merck treatment is only for adults, because it could interfere with bone and cartilage growth in children. It’s also not recommended for pregnant people, because animal studies showed there could be some effects on the fetus. Men who want to start a family should wait 90 days after the treatment, Anderson said.

“This drug works by introducing mutations and errors in that replication of the genetic material, and the concern is that it could potentially be the same thing for replication of genetic material in gametes, or sperm and new embryos,” Anderson said.

Molnupiravir will be used as an additional tool that is “limited to situations where other FDA-authorized treatments for Covid are inaccessible or are not clinically appropriate,” Cavazzoni said.

Other treatments for Covid are likely to follow.

On the same day the Pfizer treatment was authorized, a study on remdesivir published in the New England Journal of Medicine found the three-day antiviral is highly effective at avoiding hospitalization and death if given early in the course of illness.

The US government is also ordering more sotrovimab, the monoclonal antibodies from GlaxoSmithKline and Vir Biotechnology that work against the Omicron variant. The last order of sotrovimab recently shipped, but the US is ordering 1m more doses, with 300,000 to be made available in January.

Treatments for Covid should be used in addition to vaccines, not in place of them, the experts stressed. They are particularly important for people who can’t be vaccinated or who don’t mount a good response to vaccines, such as the immune-compromised and the elderly.

Pekosz worries that patients will have unrealistic expectations of the antivirals. “We’ve got to be clear to people what their expectations are. These drugs are going to keep people out of the hospital. They’re not going to make you feel better the next day as you take it. They’re not going to shorten your symptoms,” he said.

“It’s just going to keep you out of the hospital – an incredibly important thing for the high-risk groups,” Pekosz said, providing “one more weapon to help reduce the amount of disease severity, hospitalizations and deaths resulting from Covid-19.”

These medications should work well against omicron and other new variants, because unlike vaccines, they don’t target the part of the virus that tends to evolve.

There have been some concerns that Merck’s drug, which works by forcing the virus to mutate until it’s no longer effective, could drive the emergence of new variants. But experts believe this is unlikely.

“It’s really as if the antiviral drug is just taking a hammer to multiple parts of the virus and breaking multiple parts of the viral genome,” Pekosz said. In fact, molnupiravir was named for Mjölnir, Thor’s mythical hammer. “So the risk for mutations that result in other variants of concern emerging from people who are on these drugs is probably minimal.”

But Pekosz is concerned the virus could evolve to be resistant to these treatments, as has happened with some monoclonal antibodies and, in one study, remdesivir. Giving a mix of different drugs, instead of just one kind of antiviral, would probably prevent resistance, he said.

“That’s a place where the federal government may be able to really step in and broker some deals across pharmaceutical companies, to get them to work together to make multi-drug cocktails,” Pekosz said.

In the meantime, the treatments represent a “very important step forward”, Anderson said. “Now you’ve got a really effective treatment for those people that we worry about the most.”

If at-risk people are able to access the treatments quickly, “before the virus has a chance to take hold, you can basically shut down replication,” he said. “You can save that person … It’s a big deal.”