A new Covid antiviral pill was found to be as effective as Paxlovid in curbing mild to moderate disease among 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 that the treatment had fewer side effects than Paxlovid, the reference antiviral for high-risk patients. About 67% of people who took the experimental pill, called VV116, reported side effects, compared with 77% of those 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 used for insomnia, seizures or high blood pressure.
“You have a drug that seems to be just as good as Paxlovid, but less cumbersome,” said Dr. Panagis Galiatsatos, an 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 intravenous infusion. But the team behind the new drug, pharmaceutical companies Junshi Biosciences and Vigonvita Life Sciences, modified the formula so that it can be absorbed by the body in pill form, said Dr. Peter Gulick, an associate professor of medicine at Michigan State University. Gilead Sciences, which developed remdesivir, is testing a similar oral version of its drug.
Gulick said that people who have received intravenous remdesivir so far have not seen their symptoms recover in the days or weeks after treatment in the way that people on Paxlovid have.
In the VV116 trial, more than 380 people took the experimental drug, while a similarly sized group took Paxlovid. Both treatment courses lasted five days.
Median recovery time, defined as being free of Covid symptoms for two consecutive days, was four days for VV116 recipients and five days for Paxlovid recipients. 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 Thursday.
When it comes to specific side effects, about 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 that experience. Although some people in both groups had elevated levels of triglycerides (a fat in the blood that can increase the risk of heart disease or stroke), a smaller proportion of the VV116 group saw that effect: 11% compared with 21% of the group. participants who took Paxlovid.
That reduced chance of side effects is “a big problem,” Galiatsatos said.
Three quarters of trial participants were vaccinated, although the study found consistent results regardless of vaccine status.
US medical experts said it will 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 against new subvariants of omicron that have emerged since the study period.
Galiatsatos said the FDA is likely to request more data before considering emergency authorization.
But he added that the pill looks promising: “It looks like we might have another tool in the toolbox.”
Filling a gap in Covid treatments
Antiviral drugs are designed to stop the replication of a virus. 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 for the future,” he said.
In addition to remdesivir, the FDA has granted emergency authorization to two antiviral pills: Paxlovid and molnupiravir. The National Institutes of Health recommends Paxlovid, with molnupiravir as an alternative in situations where neither Paxlovid nor remdesivir is available or appropriate.
Paxlovid, while effective in preventing serious illness, does have some drawbacks. It contains a medicine called ritonavir, which can cause liver damage, mainly in patients with pre-existing liver problems, and can have negative interactions with other medicines such as statins or heart medicines.
“Many medical providers were very hesitant to use Paxlovid in many patients because they were concerned about drug interactions,” Gulick said.
Many patients at highest risk for severe covid are taking multiple medications, he added.
“Paxlovid is still a great drug, but there are a variety of reasons that prevent it from really reaching everyone you need,” Galiatsatos said.
Experts are hopeful that VV116 can fill some of these gaps, assuming it does well in larger studies. Standard Phase 3 drug trials involve up to 3,000 participants, according to the FDA. by paxlovid late stage trial included more than 2,200 people.
“Weird side effects that you’re only going to notice when you launch into a larger population,” Galiatsatos said. “It’s like playing the lottery: 1 in 100 won’t win, but 1 in a million will, because it increases the odds of a rare event happening.”