FDA advisors recommend full approval of Pfizer Covid treatment Paxlovid for adults 50 and over and other high-risk people

The Food and Drug Administration’s independent panel of advisors recommended full approval of Pfizer’s Covid-19 antiviral pill Paxlovid for high-risk adults 16-1 on Thursday, but flagged potentially harmful drug interactions.

The treatment is advised for people over 50 or those who suffer from a variety of medical conditions like high blood pressure or diabetes that place them at a higher risk of ending up in the hospital or dying from Covid.

The FDA first made Paxlovid available in December 2021 for emergency use in high-risk individuals ages 12 and up. Pfizer submitted an application for full approval of the drug in June 2022, but the FDA extended its review period for the application in December 2022. 

The agency typically follows the advice of its advisory committees but is not required to do so. It is slated to make a final decision in May. 

“I’d say besides oxygen, Paxlovid has probably been the single most important treatment tool during this epidemic and continues to be,” said Richard Murphy, chief of infectious diseases at the Veterans Affairs White River Junction Medical Center.

The panel drew on three of Pfizer’s mid-to-late-stage clinical trials on Paxlovid that enrolled more than 6,000 patients across 21 countries. 

One trial called EPIC-HR examined high-risk adults who were unvaccinated and had no prior Covid infection. The trial found Paxlovid reduced the risk of hospitalization or death by 86% in adults treated within five days of symptom onset, and 89% in those treated within three days of symptoms, according to an FDA review of the company’s data.

“I thought that the efficacy data was clear and convincing,” said Dr. Sankar Swaminathan, chief of the division of infectious diseases at the University of Utah’s School of Medicine.

But advisors agreed that serious adverse reactions due to drug-to-drug interactions, or DDIs, with Paxlovid are a key safety concern.

“I would just emphasize that we underscore the importance of risk mitigation to the prescriber, primary care, physician, and other prescribers in terms of drug-drug interactions,” said Dr. David Hardy, an adjunct clinical professor of medicine at the University of Southern California.

“That’s where I think we may get into trouble, I should say, where they would get into trouble with prescribing this medication without a good knowledge of what ritonavir does to other medications,” he said. Paxlovid is made up of two anti-viral medications, ritonavir and nirmatrelvir.

More than half of Paxlovid-eligible Medicare and Veterans Affairs patients are on medications that have drug interactions with Paxlovid, according to an FDA review of safety surveillance data. Roughly 74% of Paxlovid prescriptions were from adult primary care practitioners who may not be experienced with managing the possible adverse drug interactions, the FDA review added. 

The FDA said its office of surveillance and epidemiology recorded 271 reports of serious adverse events potentially related to drug interactions with Paxlovid, including 147 hospitalizations, as of late January. The most common drugs that cause problems were immunosuppressants, which are often used to treat HIV and organ transplant patients, the FDA said.

But Swaminathan noted that drug interactions should be “addressable and minimized.” FDA staff said earlier in the meeting that they could potentially be managed by adjusting the dose of certain drugs, increasing patient monitoring and ensuring product labeling informs prescribers and patients of potential drug interactions.

Paxlovid consists of two separate medications packaged together that are meant to reduce the risk of hospitalization or death from Covid. Nirmatrelvir blocks a key enzyme that the Covid virus needs to replicate, while ritonavir boosts the first’s medicine’s ability to fight the infection. 

Patients take Paxlovid within five days of developing Covid symptoms to reduce their risk of hospitalization or death. To complete a full course of the drug, patients must take three Paxlovid pills twice a day for five days. 

More than 12 million courses of Paxlovid have been delivered to pharmacies across the U.S. and 1.3 million doses are available nationwide, according to federal data. About 10 million patients in the U.S. and 14 million worldwide have been treated with the drug, according to Jim Rusnak, Pfizer’s chief development officer for internal medicine.

Sales of Paxlovid jumped to $18.9 billion in 2022, the first year it was available, but Pfizer expects that revenue to drop 58% to $8 billion this year. 

The single vote against Paxlovid was from Terry Gillespie, a patient representative from Plainfield, Ill. Gillespie raised concerns about doctors not knowing when to prescribe the drug, noting that they had a Covid infection four to five times “but never once” was offered Paxlovid.

“I don’t feel that the doctors really know how to use it,” Gillespie said.

Following the vote, Swaminathan also noted that he had a “distressingly large number of patients” whose doctors discouraged them from taking Paxlovid due to fears of rebound Covid cases. That’s when patients see their Covid symptoms or a positive test return after initially recovering.

“I am concerned that there’s not a good understanding in the medical community, and an actual dissuading of patients from taking an effective drug that could save their life,” he said

Reports of those cases cropped up not long after Paxlovid entered the market in 2021, with President Joe Biden and his former chief medical advisor Dr. Anthony Fauci seemingly recovered from Covid after taking the anti-viral cocktail before testing positive again.

Swaminathan said there’s a “dramatic acceptance” among the media that Paxlovid causes rebound cases and are “potentially worse” than what you had before taking the drug, despite a lack of data supporting that belief.

Dr. Lindsey Baden, the chairperson of the panel and director of the Brigham and Women’s Hospital, added that emerging data indicates Paxlovid caused rebound cases are “not the biology of what is going on.”

“Up until very recently, and even some of the data shared today have helped me understand what it means. So we are seeing data in real-time that are systematic and informative,” Baden said.

An FDA review of Pfizer’s clinical trials found overall rates of rebound ranged from 10% to 16%, “with no evidence of a higher rate of symptom rebound or moderate symptom rebound” in patients who received Paxlovid compared to a placebo. That was also regardless of patients’ risk of severe disease, or whether omicron variant or an earlier strain was dominant, according to the agency’s staff.