FDA committee supports approval of COVID-19 treatment Paxlovid for high-risk adults
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Key takeaways:
- The FDA’s Antimicrobial Drugs Advisory Committee voted that the overall risk-benefit of Paxlovid is favorable for adults at high risk for severe disease.
- A trial found that Paxlovid was not associated with COVID-19 rebound.
The FDA’s Antimicrobial Drugs Advisory Committee voted Thursday to support the approval of Paxlovid for the treatment of mild-to-moderate COVID-19 in adults at high risk for severe disease, hospitalization or death.
The committee voted 16-1 that the benefits of Paxlovid outweigh the risks in this population. The FDA will take the vote into consideration while making its final decision on approval, which is expected in May.
Paxlovid was granted an emergency use authorization by the FDA in December 2021 for people aged 12 years or older who test positive for SARS-CoV-2 and are at risk for severe disease. In July 2022, the FDA expanded the EUA to allow pharmacists to prescribe the drug to qualifying people immediately after testing positive for the virus.
During Thursday’s meeting, the FDA said it is looking at widening the number of people eligible for a prescription, and recommending those prescriptions be made earlier after infection.
In three phase 2/3 trials presented to the committee, no major safety concerns were identified for Paxlovid, although there are risks for serious adverse reactions due to drug-drug interactions (DDIs) — some medications must be stopped, whereas others only need dose adjustments. The DDIs should be included in labeling for Paxlovid.
In addition to efficacy against the delta variant of SARS-CoV-2, data showed that Paxlovid retained antiviral activity against the omicron variant and its major subvariants. Pfizer and the FDA said that, despite limited trial data assessing clinical efficacy against omicron, evidence suggests it is reasonable to conclude that the drug will remain effective against omicron.
“This is clinically meaningful for most individuals, although clearly it’s important to weigh the DDIs and the risks that they pose,” Adaora Adimora, MD, MPH, FIDSA, the Sarah Graham Kenan Distinguished Professor of Medicine at the University of North Carolina School of Medicine and an Infectious Disease News Editorial Board Member, said during the meeting.
“It’s also clinically meaningful for the population as a whole given the high incidence of COVID-19 in the U.S. that is ongoing. And it’s especially important given the limited availability of effective oral agents,” Adimora said.
The FDA and Pfizer found no association between Paxlovid and so-called “rebound” COVID-19, with trial data showing that viral RNA rebound and symptom rebound occurred at similar frequencies in participants who received Paxlovid and placebo.
“The applicant has shown that, as the COVID-19 pandemic has evolved with new and different variants of concern, that [there is] continued benefit in terms of the most severe outcomes of hospitalization and death,” Infectious Disease News Editorial Board Member David W. Hardy, MD, said during the meeting. “So, although they definitely did not reach [the study] endpoints, it is still showing a degree of benefit I think is necessary.”
The committee did not consider the risk-benefit of Paxlovid for children aged 12 years or older on Thursday. The FDA said the EUA for this age group will remain in place, although some members of the committee expressed support for an approval for that age group as well.
References:
- FDA. FDA briefing document. https://www.fda.gov/media/166197/download. Accessed March 16, 2023.
- FDA advisory committee votes in support of favorable benefit-risk profile for Pfizer’s Paxlovid. https://www.pfizer.com/news/press-release/press-release-detail/fda-advisory-committee-votes-support-favorable-benefit-risk. Published March 16, 2023. Accessed March 16, 2023.
Perspective
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Based on how the FDA briefing document was prepared, emphasizing the positive findings and burying the negative findings, [there is a] 100% probability of a positive Antimicrobial Drugs Advisory Committee recommendation and FDA approval of Paxlovid.
Approval will likely occur in the current vague “high-risk” patient criteria. The benefit is clearly less in vaccinated or low-risk populations.
In the EPIC-SR “standard risk” trial, there were eight serious adverse events — typically, hospitalizations — with Paxlovid versus 11 with placebo. This is a 0.5% absolute difference in serious adverse events — ie, likely all-cause hospitalization.
No COVID-related hospitalizations were reported during the omicron period of the EPIC-SR trial among 287 additional randomized participants who were not included in the overall results. Serious adverse events in these 287 are excluded from the results provided.
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FDA. Updated information: March 16, 2023: Antimicrobial Drugs Advisory Committee meeting announcement. https://www.fda.gov/advisory-committees/advisory-committee-calendar/updated-information-march-16-2023-antimicrobial-drugs-advisory-committee-meeting-announcement. Updated March 15, 2023. Accessed March 16, 2023.
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