What’s next for COVID-19 drugs?

Updates on Paxlovid, Moderna’s mRNA vaccine, and more.

Paxlovid, an antiviral approved to treat COVID-19 in high-risk populations, has underperformed in a new trial — but promising new COVID-19 drugs are now being authorized or in the works.

The challenge: COVID-19 might not be a global health emergency anymore, but it’s still a serious public health issue — every week in the US, thousands of people are being hospitalized with the virus, and hundreds or thousands will die from it. 

To get those numbers down, and to prepare for the possibility of mutations that make the virus more deadly or contagious, we need new (and better) COVID-19 preventatives and treatments. 

Vaccinated or not, if you get sick, you don’t have many treatment options.

When the first COVID-19 vaccines were approved, they were more than 95% effective against infection with the virus. Today’s shots hover around 50-60% efficacy, however. Being vaccinated does reduce the risk of a severe illness after infection, but even a mild to moderate case of COVID-19 can be hugely unpleasant.

Vaccinated or not, if you do get sick, you don’t have many treatment options. The FDA has authorized just three COVID-19 treatments over the past four years, and new trial results suggest that one of them — Paxlovid — might not be as useful as once hoped.

The drug: Paxlovid is a combination of two drugs — nirmatrelvir and ritonavir — that work together to prevent the coronavirus from replicating in the body. In December 2021, it became the first oral COVID-19 treatment to be granted an emergency use authorization (EUA) by the FDA. 

That EUA was based on the results of a trial of about 2,000 unvaccinated adults who were either over the age of 60 or had at least one medical condition that put them at high risk of developing severe COVID-19. It found that Paxlovid could reduce the risk of hospitalization or death by 88% compared to a placebo if administered within 5 days of symptom onset.

Since then, the FDA has fully approved Paxlovid, and it is currently available to people 12 years and older if they have higher than normal risk of developing severe COVID-19.

In the new trial, Paxlovid ended up performing about the same as the placebo.

The trial: On April 3, researchers published the results of a new randomized controlled trial of Paxlovid, involving about 1,300 people. This one included vaccinated people with risk factors for severe COVID-19, and people at normal risk who were either unvaccinated or hadn’t received a shot in the past year.

The primary goal of the trial was to see if Paxlovid could reduce the amount of time people had with symptoms, but it ended up performing about the same as the placebo.

The researchers also looked at the drug’s ability to prevent COVID-related hospitalization or death from any cause, within 28 days of a person starting on the drug. While there were fewer of those cases in the treatment group (5) than in the placebo group (10), this difference wasn’t enough to be statistically significant.

The big picture: Based on these new results, it seems Paxlovid is only likely to make a difference for the kinds of people involved in the initial trial: unvaccinated and at high risk of severe illness. 

Still, other COVID-19 drugs that could work in larger populations or serve different purposes are in the works.

A treatment approved in China — simnotrelvir — has been shown to speed up symptom relief in people at average risk of severe illness. There is no word yet on whether its maker plans to apply for approval in the US, though, and it would likely need to run another trial in the US to get FDA approval. 

It might soon be easier for to avoid getting sick altogether.

However, the FDA has fast-tracked its review of the Japanese antiviral ensitrelvir, which appears to speed up symptom relief and shorten the duration of a COVID-19 infection in people with mild to moderate COVID-19 and no risk factors for severe illness.

The FDA also recently authorized a new drug called Pemgarda as a COVID-19 preventative in people who have a compromised immune system — this not only puts them at high risk of severe infection, it reduces their ability to respond to vaccination.

Moderna, meanwhile, announced in March that an updated version of its mRNA vaccine for COVID-19 triggered a stronger immune response than its current shot in a phase 3 trial — meaning it might soon be easier for us to avoid getting sick altogether.

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