Paxlovid Misses in Standard-Risk COVID-19June 15, 2022
Updated findings from a nirmatrelvir/ritonavir (Paxlovid) trial in standard-risk COVID-19 suggest the antiviral’s benefits are less clear for those not at high risk of severe outcomes.
As was previously reported, Pfizer’s so-called EPIC-SR (standard risk) trial failed to meet its primary endpoint: a relative risk reduction in self-reported, sustained alleviation of all symptoms for 4 consecutive days.
In the updated analysis reported by the company via press release, a non-significant 51% reduction was observed for the secondary endpoint of hospitalization or death with nirmatrelvir/ritonavir. Of 1,153 patients enrolled through December 2021, there were five incidents of hospitalization or death with the drug versus 10 with placebo (0 vs 1 death, respectively).
A subgroup analysis of 721 vaccinated adults — all of whom had at least one risk factor for progression to severe disease — showed a non-significant 57% reduction in hospitalization or death with the drug versus placebo (3 vs 7).
Pfizer also reported a “nominally significant” 62% drop in the prespecified secondary endpoint of COVID-related medical visits per day with the drug compared with placebo (P=0.0228) in the full study population. These visits included emergency department, urgent care, hospital admission, and telehealth calls, among others.
Another prespecified analysis showed a 72% reduction in the average number of days in the hospital for those who got nirmatrelvir/ritonavir, the company reported. There was also a trend indicating an advantage in ICU admission with the drug, but this was not significant.
Adverse events were comparable, at about 23% in both groups, and most were mild. Serious adverse events were also comparable, at 1.4% with the drug and 1.9% with placebo.
Pfizer said it’s ending enrollment in EPIC-SR due to the low rate of hospitalization and death in patients at standard risk from COVID-19, and the company will focus on gathering data on the drug in vulnerable populations, including longer treatment durations in immunocompromised patients and hospitalized patients with severe disease.
Jeremy Faust, MD, an emergency physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of MedPage Today, had previously raised concerns that Paxlovid may be being misused. Anecdotally, he said, most patients who take it don’t have a significant risk of developing severe illness, and have been vaccinated if not boosted or double-boosted.
In his newsletter Inside Medicine, Faust noted that the EPIC-HR trial, which was published in the New England Journal of Medicine, did not include vaccinated patients, and was focused on high-risk patients — so the 89% reduced risk of progression to severe COVID-19 (including hospitalization and death) pertains to high-risk unvaccinated patients.
Early data are starting to show that most people who are vaccinated, especially those who are under 65, are unlikely to benefit from the drug, Faust said. Two studies from Israel — one preprint and another published in Clinical Infectious Diseases — show that the drug didn’t hold advantages for younger patients, he said.
The downsides to unnecessary use of the drug include risk of rebound (which is still being characterized), and the potential for development of resistant strains, Faust wrote.