Coronavirus disease (COVID-19) treatment pill Paxlovid is seen in boxes, at Misericordia hospital in Grosseto, Italy, February 8, 2022.
Jennifer Lorenzini | Reuters
The Food and Drug Administration’s independent panel of advisors beneficial 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 suggested for people over 50 or those that suffer from medical conditions similar to hypertension or diabetes that place them at a better risk of ending up within 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, however the FDA prolonged its review period for the appliance in December.
The agency typically follows the recommendation of its advisory committees but will not be required to achieve this. It’s slated to make a final decision in May.
“I’d say besides oxygen, Paxlovid has probably been the one most significant treatment tool during this epidemic and continues to be,” said Richard Murphy, chief of infectious diseases on the Veterans Affairs White River Junction Medical Center.
The panel, which voted 16-1 to recommend the complete approval, drew on three of Pfizer’s mid- to late-stage clinical trials on Paxlovid that enrolled greater 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 chance of hospitalization or death by 86% in adults treated inside five days of symptom onset, and 89% in those treated inside three days of symptom onset, in accordance with an FDA review of the corporate’s data.
“I assumed that the efficacy data was clear and convincing,” said Dr. Sankar Swaminathan, chief of the division of infectious diseases on the University of Utah’s School of Medicine.
Dr. Adaora Adimora, a professor within the department of infectious diseases on the University of North Carolina School of Medicine, called the chance reduction in Pfizer’s trials “clinically meaningful” for most people and the broader population at a time when the U.S. still sees hundreds of Covid cases each week. About 200,000 Covid cases are reported weekly nationwide, in accordance with the Centers for Disease Control and Prevention.
But advisors agreed that serious hostile reactions attributable to interactions between Paxlovid and other drugs are a key safety concern.
This photo taken on July 31, 2022 shows a medical examiner taking a swab sample from a lady to be tested for the Covid-19 coronavirus at a swab collection site in Guangzhou, in China’s southern Guangdong province. Around a 3rd of individuals with Covid will experience a rebound of their symptoms, no matter whether or not they’ve been treated with the antiviral Paxlovid, in accordance with a study posted online Tuesday.
Str | Afp | Getty Images
“I’d just emphasize that we underscore the importance of risk mitigation to the prescriber, primary care, physician, and other prescribers when it comes to drug-drug interactions,” said Dr. David Hardy, an adjunct clinical professor of drugs on the University of Southern California.
“That is where I believe we may get into trouble, I should say, where they might get into trouble with prescribing this medication without a very good knowledge of what ritonavir [one of the medications in Paxlovid] does to other medications,” he said.
Greater than half of Paxlovid-eligible Medicare and Veterans Affairs patients are on medications which have drug interactions with Paxlovid, in accordance with an FDA review of safety surveillance data. Roughly 74% of Paxlovid prescriptions were from adult primary care practitioners who might not be experienced with managing the possible hostile drug interactions, the FDA review added.
The FDA said its office of surveillance and epidemiology recorded 271 reports of significant hostile events potentially related to drug interactions with Paxlovid, including 147 hospitalizations and 6 deaths, as of late January. Probably the most common drugs that caused problems were immunosuppressants, which are sometimes used to treat HIV and organ transplant patients, the FDA said.
But Swaminathan noted that drug interactions needs to be “addressable and minimized.” FDA staff said earlier within 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 copy, and ritonavir, which boosts the primary medication’s ability to fight the infection.
Patients take Paxlovid inside five days of developing Covid symptoms to scale back their risk of hospitalization or death. To finish a full course of the drug, patients must take three Paxlovid pills twice a day for five days.
Greater than 12 million courses of Paxlovid have been delivered to pharmacies across the U.S. and 1.3 million doses can be found nationwide, in accordance with federal data. About 10 million patients within the U.S. and 14 million worldwide have been treated with the drug, in accordance with Jim Rusnak, Pfizer’s chief development officer for internal medicine.
Sales of Paxlovid jumped to $18.9 billion in 2022, the primary 12 months it was available, but Pfizer expects that revenue to drop 58% to $8 billion in 2023.
The one 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 that they had a Covid infection 4 to 5 times “but never once” was offered Paxlovid.
“I do not feel that the doctors really know learn how to use it,” Gillespie said.
Following the vote, Swaminathan said that he had a “distressingly large variety of patients” whose doctors discouraged them from taking Paxlovid attributable to fears of rebound Covid cases. That is when patients see their Covid symptoms return or get a positive test after they initially get well.
“I’m concerned that there is not a very good understanding within the medical community and an actual dissuading of patients from taking an efficient drug that might 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 is a “dramatic acceptance” among the many media that Paxlovid causes rebound cases and that they’re “potentially worse” than patients had before taking the drug, despite an absence of knowledge 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 occurring.”
“Up until very recently, and even a number of the data shared today have helped me understand what it means. So we’re seeing data in real time which can be 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 better rate of symptom rebound or moderate symptom rebound” in patients who received Paxlovid compared with patients who received a placebo. That was also no matter patients’ risk of severe disease, or whether the omicron variant or an earlier strain was dominant, in accordance with the agency’s staff.
Prior to the panel’s vote, FDA staff said more data is required to find out if immunocompromised people need an extended course of Paxlovid that goes beyond the standard five days. They cited an overall lack of clinical trial data on using Paxlovid in those people, noting that only 13 of the greater than 2,000 patients within the EPIC-HR trial had weakened immune systems.
The FDA staff said immunocompromised people might profit more from longer courses of Paxlovid because they usually tend 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 no less than 20 days. Roughly 7 million U.S. adults are immunocompromised, the CDC estimates.
Representatives from Pfizer highlighted the corporate’s ongoing efforts to research using Paxlovid in immunocompromised patients. In September, the corporate began 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 on the University of Washington, said she’s “pretty satisfied” with the corporate’s plan, but noted that she hopes the HIV population is included in clinical trials.
“I hope that the studies could be done in a timely way, because we want this information pretty badly,” Carvalho said.