FDA advisers vote to approve Paxlovid for Covid-19 treatment in high-risk adults


Advisors to the U.S. Food and Drug Administration voted 16-1 on Thursday to fully approve Paxlovid, saying the benefits outweigh the drug’s risks for treating mild-to-moderate Covid-19 in adults at high risk for severe outweighs illness, including hospitalization and death.

Before the antiviral drug is fully approved, the FDA — which usually follows the recommendations of the independent advisory committee — must conduct its own review. That should end in May.

Over 8 million people in the US have received Paxlovid, a combination of the drugs Nirmatrelvir and ritonavir since it became available under an emergency use authorization in December 2021.

“I would say that along with oxygen, Paxlovid has probably been, and continues to be, the most important single tool in this epidemic,” said Dr. Richard Murphy, chief of infectious diseases at Veterans Affairs White River Junction Medical Center and a member of the FDA’s Antimicrobial Drugs Advisory Committee, who voted for approval at the meeting.

“We still have many groups that could benefit from using Paxlovid, including unvaccinated people, unvaccinated people, the elderly, people with compromised immune systems, and the other treatment options that we have have significant disadvantages,” he said.

Data from phase 2 and 3 clinical trials support the efficacy of Paxlovid regardless of Covid vaccination status or previous infection, the FDA said in documents released ahead of Thursday’s meeting. The agency also said it was reasonable to conclude, despite limited data, that in high-risk adults with Covid infection caused by the omicron variant of coronavirus, like previous variants, Paxlovid is “probably the clinical retains effectiveness”.

“I found the efficacy data clear and compelling,” said Dr. Shankar Swaminathan, chief of the infectious diseases division at the University of Utah School of Medicine, who voted Thursday to approve. “I think the fact that the drug has retained its activity against different evolutionary strains of the virus is also reassuring and gives hope that it will continue to be so in the future.”

The FDA also concluded that Paxlovid is not associated with a Covid-19 rebound, in which people test positive or their symptoms return after completing the drug’s five-day cycle.

The agency said it reviewed data on rebound cases that some users have reported since Paxlovid was approved in 2021. Last year, both President Biden and his former chief medical adviser, Dr. Anthony Fauci, of rebound symptoms after taking Paxlovid.

However, based on clinical trial data, the FDA “has not found a clear association between Paxlovid treatment and Covid-19 rebound.”

Covid rebound rates ranged from 10% to 16%, with no difference between people taking Paxlovid and those taking a placebo. This was also independent of an individual’s risk of serious disease with the Omicron variant compared to the Delta variant, according to FDA-reviewed clinical study data.

Overall, the agency said, the results suggest that a rebound of Covid-19 may occur in a subset of infections as part of the disease’s natural progression and resolution.

No major safety concerns were identified in the clinical study data, the FDA said. However, the agency has flagged 137 drugs with Paxlovid drug interactions (DDIs) that can lead to serious side effects.

According to an FDA Emergency Use Authorization Fact Sheet, Paxlovid can stop the body from metabolizing certain drugs, resulting in higher drug concentrations that can lead to serious or life-threatening reactions. Medications that should not be taken with Paxlovid include some medications used to treat conditions such as high cholesterol, gout, migraines, irregular heartbeat, and benign prostatic hyperplasia.

According to the agency, over 50% of Paxlovid-eligible patients may be taking medication with a DDI at the time of Covid diagnosis.

“I just want to emphasize that we underscore the importance of risk reduction for the prescriber, GP and other prescribers in terms of drug-drug interactions,” said Dr. FDA Committee Member David Hardy, Associate Clinical Professor at the Keck School of Medicine at the University of Southern California, who voted in favor of the approval. “That’s where I think we could get into trouble — or I can tell where they can get into trouble — if we’re prescribing this drug without knowing exactly what ritonavir does to other drugs.”

The committee said the benefits of Paxlovid may not outweigh the risk of adverse drug reactions in all patients. In people at high risk for severe Covid-19, DDIs can be managed by stopping the drug, adjusting the dose, or increasing monitoring.

Clinical trials of the safety and effectiveness of Paxlovid in children, pregnant women and people with compromised immune systems are ongoing.

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