A new antiviral pill for Covid has been shown to be as effective as Paxlovid in curbing mild to moderate illness in people at high risk of severe disease in a phase 3 trial in China.
The results, published Wednesday in the New England Journal of Medicine, suggest the treatment had fewer side effects than Paxlovid, the gold standard antiviral for high-risk patients. About 67% of people who took the experimental pill, called VV116, reported side effects, compared to 77% who took Paxlovid.
The new pill was also less likely than Paxlovid to cause unexpected side effects due to reactions with other drugs, such as those for insomnia, seizures or high blood pressure.
“You have a drug that seems to be as good as Paxlovid, but less cumbersome,” said Dr. Panagis Galiatsatos, assistant professor of medicine at Johns Hopkins Medicine in Baltimore.
VV116 is similar to the antiviral remdesivir, which the Food and Drug Administration has approved as an IV infusion. But the team behind the new drug – pharmaceutical companies Junshi Biosciences and Vigonvita Life Sciences – tweaked the formula so the body could absorb it in pill form, said Dr Peter Gulick, associate professor of medicine. at Michigan State University. Gilead Sciences, which developed remdesivir, is testing a similar oral version of its drug.
Gulick said people who have received remdesivir intravenously so far have not seen their symptoms rebound within days or weeks of treatment like people have with Paxlovid.
In the VV116 trial, more than 380 people took the experimental drug, while a similarly sized group took Paxlovid. Both cures lasted five days.
Median recovery time – defined as no Covid symptoms for two consecutive days – was four days for VV116 recipients and five days for those who took Paxlovid. After four weeks, around 98% of all participants had recovered and no one developed severe Covid.
Study co-author Ren Zhao, a professor at Shanghai Jiao Tong University School of Medicine, called the trial a “great success” in a press release on Thursday.
As for specific side effects, around 26% of trial participants who took Paxlovid said it altered their sense of taste – food tasted sour, sweet, bitter or metallic – but only 4 % of people who took VV116 reported this experience. Although some people in both groups had high levels of triglycerides (fats in the blood that can increase the risk of heart disease or stroke), a smaller proportion of those in the VV116 group saw this effect: 11% compared to 21% of participants who took Paxlovid.
This reduced likelihood of side effects is “a big deal,” Galiatsatos said.
Three-quarters of trial participants were vaccinated, although the study found consistent results regardless of vaccination status.
American medical experts said it would be important to study the pill in a larger and more diverse group. Such trials could better detect rare side effects and examine how the drug holds up to new omicron subvariants that have emerged since the study period.
Galiatsatos said the FDA would likely request more data before considering emergency clearance.
But he added that the pill looks promising: “Looks like we might have another tool in the toolbox.”
Filling a gap in Covid treatments
Antiviral drugs are designed to stop a virus from replicating. Because they don’t stimulate an antibody response like vaccines do, the effectiveness of antivirals is less sensitive to changes in the coronavirus as new variants and subvariants evolve, according to Gulick.
“This whole group of agents is going to be very important going forward,” he said.
Besides remdesivir, the FDA has granted emergency clearance to two antiviral pills: Paxlovid and molnupiravir. The National Institutes of Health recommend Paxlovid, with molnupiravir as an alternative in situations where neither Paxlovid nor remdesivir is available or appropriate.
Paxlovid, although effective in preventing serious illnesses, has a few drawbacks. It contains a drug called ritonavir, which can damage the liver – mainly in patients with pre-existing liver problems – and it may have negative interactions with other drugs such as statins or heart medications.
“Many medical providers were very hesitant to use Paxlovid in many patients because they were concerned about drug interactions,” Gulick said.
Many patients most at risk of severe Covid take multiple drugs, he added.
“Paxlovid is still a great drug, but there are a variety of reasons why it doesn’t really reach everyone it needs,” Galiatsatos said.
Experts hope VV116 could fill in some of these gaps, assuming it works well in larger studies. According to the FDA, standard phase 3 drug trials involve up to 3,000 participants. Paxlovid’s late-stage trial included more than 2,200 people.
“Rare side effects that you won’t experience until you get into a larger population,” Galiatsatos said. “It’s like playing the lottery: 1 in 100 isn’t going to win, but 1 in a million will, because you’re increasing your chances of a rare event happening.”