Advisors to the U.S. Food and Drug Administration voted 16 to 1 on Thursday to support the full approval of Paxlovid, stating that the benefits outweigh any risks of the drug for treating mild to moderate Covid-19 in adults who have a are at high risk of serious illness, including hospitalization and death.
Before the antiviral medication is fully approved, the FDA – which generally follows the recommendations of the independent advisory committee – must conduct its own review. That is expected to be completed in May.
More than 8 million people in the US have received Paxlovid, a combination of the drugs nirmatrelvir and ritonavir, since it became available under emergency use authorization in December 2021.
“I would say Paxlovid has probably been the most important tool in this epidemic next to oxygen, and it still is,” said Dr. Richard Murphy, chief of infectious diseases at the Veterans Affairs White River Junction Medical Center and a member of the Antimicrobial Drugs. FDA Advisory Committee, which voted for approval at the meeting.
“We still have many groups that could benefit from using Paxlovid, including unvaccinated individuals, undervaccinated individuals, the elderly, the immunocompromised, and the other treatment options we have have significant drawbacks,” he said.
Data from Phase 2 and 3 clinical trials support Paxlovid’s efficacy regardless of Covid vaccination status or previous infection, the FDA said in documents released ahead of Thursday’s meeting. The agency also said it is reasonable to conclude, despite limited data, that Paxlovid is “likely to maintain clinical efficacy” in high-risk adults with Covid infection caused by the Omicron variant of the coronavirus, as with previous variants.
“I thought the efficacy data was clear and compelling,” said Dr. Shankar Swaminathan, chief of infectious diseases at the University of Utah School of Medicine, who voted for approval Thursday. “I think the fact that the drug has remained effective against several evolutionary strains of the virus is also reassuring and gives hope that it will continue to do so in the future.”
The FDA also concluded that Paxlovid is not associated with Covid-19 rebound, with people testing positive or seeing their symptoms return after they finish the five-day course of the drug.
The agency said it has reviewed data on rebound cases, which some users have reported since Paxlovid was authorized in 2021. Last year, both President Biden and his former chief medical advisor, Dr. Anthony Fauci, rebound symptoms after taking Paxlovid.
However, based on data from clinical trials, the FDA has “established no clear association between Paxlovid treatment and the rebound of Covid-19.”
Covid rebound rates ranged from 10% to 16%, with no difference between people taking Paxlovid and those taking a placebo. This was also regardless of a person’s risk of serious illness with the Omicron variant compared to the Delta variant, according to data from clinical trials reviewed by the FDA.
Overall, the agency said, the findings indicate that Covid-19 rebound may occur in a subset of infections as part of the natural progression and resolution of the disease.
No major safety concerns were identified in the clinical trial data, according to the FDA. However, the agency has flagged 137 medications with Paxlovid drug interactions (DDIs) that can lead to serious side effects.
Paxlovid can stop the body from metabolizing certain medications, leading to higher drug concentrations that can lead to serious or life-threatening reactions, according to an FDA Emergency Use Authorization Fact Sheet. Medicines that should not be taken with Paxlovid include some medicines used to treat conditions such as high cholesterol, gout, migraines, irregular heartbeat, and benign prostatic hyperplasia.
According to the agency, more than 50% of Paxlovid-eligible patients may be taking medication with a DDI at the time of Covid diagnosis.
“I would just like to emphasize that we underline the importance of risk reduction for the prescriber, primary care physicians and other prescribers in terms of drug interactions,” said FDA committee member Dr. David Hardy, an adjunct clinical professor at the Keck School of Medicine at the University of Southern California, who voted in favor. “That’s where I think we could get into trouble — or say where they might get into trouble — prescribing this drug without really knowing what ritonavir does to other drugs.”
The committee said the benefits of Paxlovid may not outweigh the risk of side effects in all patients. For those at high risk for severe Covid-19, DDIs can be managed by holding the drug, adjusting the dose, or increasing monitoring.
Clinical trials on the safety and effectiveness of Paxlovid in children, people who are pregnant, and people with weakened immune systems are ongoing.