- The FDA's independent panel of advisors recommended full approval of Pfizer's Covid antiviral treatment Paxlovid for adults who are at high risk of getting severely sick with 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.
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 on Thursday but flagged potentially harmful drug interactions.
The treatment is advised for people over 50 or those who suffer from medical conditions such as 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.
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, which voted 16-1 to recommend the full approval, 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 symptom onset, 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.
Dr. Adaora Adimora, a professor in the department of infectious diseases at the University of North Carolina School of Medicine, called the risk reduction in Pfizer's trials "clinically meaningful" for most individuals and the broader population at a time when the U.S. still sees thousands of Covid cases each week. About 200,000 Covid cases are reported weekly nationwide, according to the Centers for Disease Control and Prevention.
But advisors agreed that serious adverse reactions due to interactions between Paxlovid and other drugs 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 [one of the medications in Paxlovid] does to other medications," he said.
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 and six deaths, as of late January. The most common drugs that caused 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 interactions 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 medications: nirmatrelvir, which blocks a key enzyme that the Covid virus needs to replicate, and ritonavir, which boosts the first medication'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 in 2023.
The single vote against Paxlovid was from Terry Gillespie, a patient representative from Plainfield, Illinois. 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 said 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 return or get a positive test after they initially recover.
"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 antiviral cocktail before testing positive again.
Swaminathan said there's a "dramatic acceptance" among the media that Paxlovid causes rebound cases and that they are "potentially worse" than patients 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 with patients who received a placebo. That was also regardless of patients' risk of severe disease, or whether the omicron variant or an earlier strain was dominant, according to the agency's staff.
Prior to the panel's vote, FDA staff said more data is needed to determine if immunocompromised people need a longer course of Paxlovid that goes beyond the traditional five days. They cited an overall lack of clinical trial data on the use of Paxlovid in those people, noting that only 13 of the more than 2,000 patients in the EPIC-HR trial had weakened immune systems.
The FDA staff said immunocompromised people might benefit more from longer courses of Paxlovid because they are more likely to have prolonged Covid infections. The Centers for Disease Control and Prevention says immunocompromised patients may remain infectious beyond 20 days of symptom onset, and recommends those patients isolate for at least 20 days. Roughly 7 million U.S. adults are immunocompromised, the CDC estimates.
Representatives from Pfizer highlighted the company's ongoing efforts to research the use of Paxlovid in immunocompromised patients. In September, the company started enrolling those patients in a clinical trial that examines different durations of a Paxlovid course, including 10- and 15-day courses.
Dr. Paula Carvalho, a professor at the University of Washington, said she's "pretty satisfied" with the company's plan, but noted that she hopes the HIV population is included in clinical trials.
"I hope that the studies can be done in a timely way, because we need this information pretty badly," Carvalho said.