FDA advisers recommend full approval of Pfizer’s Covid drug Paxlovid

The pill Paxlovid, used to treat coronavirus disease (COVID-19), is seen in boxes at the Misericordia hospital in Grosseto, Italy, February 8, 2022.

Jennifer Lorenzini | Reuters

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

The treatment is recommended for people over the age of 50 or those suffering from conditions such as high blood pressure or diabetes that put them at a higher risk of ending up in hospital or dying from Covid.

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

The agency generally follows the advice of its advisory committees, but is not obliged to do so. A final decision will be made in May.

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

The panel, which voted 16-1 to recommend full approval, was based on three of Pfizer’s mid- to late-stage clinical trials of Paxlovid, which enrolled more than 6,000 patients in 21 countries.

“Clinically meaningful” risk reduction

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

“I found the efficacy data clear and compelling,” said Dr. Sankar Swaminathan, chief of the Department of Infectious Diseases at the University of Utah 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 studies “clinically meaningful” for most individuals and the general population at a time when the US is still seeing thousands of Covid cases per week. About 200,000 Covid cases are being reported weekly nationwide, according to the Centers for Disease Control and Prevention.

However, the advisors agreed that serious side effects due to interactions between Paxlovid and other drugs are an important safety issue.

Photo taken on July 31, 2022 shows a health worker taking a swab sample from a woman to test for the Covid-19 coronavirus at a swab collection center in Guangzhou, southern Guangdong province. About a third of people with Covid will experience recovery in their symptoms regardless of whether they have been treated with the antiviral Paxlovid, according to a study published online on Tuesday.

St. | AFP | Getty Images

“I just want to emphasize that we underscore the importance of risk reduction for the prescriber, primary care provider, physician and other prescribers in relation to drug-drug interactions,” said Dr. David Hardy, associate clinical professor of medicine at the University of Southern California.

“That’s where I think we could get in trouble, I should say where they would get in trouble if they prescribe this drug without a good knowledge of what ritonavir is [one of the medications in Paxlovid] with other drugs,” he said.

Interactions with other drugs

More than half of Paxlovid-eligible Medicare and Veterans Affairs patients take medications that have drug-drug interactions with Paxlovid, according to an FDA review of safety surveillance data. About 74% of Paxlovid prescriptions came from adult primary care physicians who may not have experience managing 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-drug interactions with Paxlovid at the end of January, including 147 hospitalizations and six deaths. The most common drugs that caused problems were immunosuppressants, which are commonly used to treat HIV and organ transplant patients, the FDA said.

But Swaminathan noted that drug interactions should be “responsive and minimized.” FDA officials said at the beginning of the meeting that drug interactions could potentially be managed by adjusting the dose of certain drugs, increasing patient monitoring, and ensuring that product labeling informs prescribers and patients about potential drug interactions.

Paxlovid is made up of two drugs: nirmatrelvir, which blocks a key enzyme the Covid virus needs to replicate, and ritonavir, which boosts the first drug’s ability to fight the infection.

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

According to federal data, more than 12 million cycles of Paxlovid have been shipped to pharmacies in the United States, and 1.3 million doses are available nationwide. About 10 million patients in the US and 14 million worldwide have been treated with the drug, according to Jim Rusnak, Pfizer’s chief development officer for internal medicine.

Paxlovid’s sales rose to $18.9 billion in 2022, the first year it was available, but Pfizer expects sales to fall 58% to $8 billion in 2023.

rebound cases

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

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

After the vote, Swaminathan said he had a “worryingly large number of patients” whose doctors advised them not to take Paxlovid for fear of renewed Covid cases. Then patients will see their Covid symptoms return or get a positive test after initially recovering.

“I am concerned that there is not a good understanding in the medical community and patients are actually being discouraged from taking an effective drug that could save their lives,” he said.

Reports of these cases surfaced shortly after Paxlovid launched in 2021, with President Joe Biden and his former chief medical adviser Dr. Anthony Fauci appeared to have recovered from Covid after taking the antiviral cocktail before testing positive again.

Swaminathan said there is “dramatic acceptance” in the media that Paxlovid causes rebound cases and that they are “potentially worse” than patients before taking the drug, although there is a lack of data to support this assumption.

dr Lindsey Baden, the panel chair and director of Brigham and Women’s Hospital, added that new data suggests Paxlovid-induced rebound cases “are not the biology of what’s going on.”

“Until recently, even some of the data shared today helped me understand what that means. So we’re seeing real-time data that’s systematic and informative,” Baden said.

An FDA review of Pfizer’s clinical trials found that 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 receiving Paxlovid in comparison to patients who received a placebo. This is also independent of the patient’s risk of serious illness or whether the Omicron variant or an earlier strain is dominant, according to the agency’s staff.

More data needed in immunocompromised patients

Ahead of the panel’s vote, FDA officials said more data is needed to determine whether immunocompromised individuals require prolonged treatment with Paxlovid beyond the traditional five days. They pointed to a general lack of clinical trial data on the use of Paxlovid in these individuals, noting that only 13 of the more than 2,000 patients in the EPIC-HR trial had a compromised immune system.

FDA staffers said immunocompromised people may benefit more from longer treatments with Paxlovid because they are more likely to have prolonged Covid infections. The Centers for Disease Control and Prevention says immunocompromised patients can remain infectious for more than 20 days after symptoms appear, and recommends isolating those patients for at least 20 days. Around 7 million US adults are immunocompromised, the CDC estimates.

Pfizer officials highlighted the company’s ongoing efforts to explore the use of Paxlovid in immunocompromised patients. In September, the company began enrolling these patients in a clinical trial examining different lengths of Paxlovid courses, including 10-day and 15-day courses.

dr Paula Carvalho, a professor at the University of Washington, said she was “fairly pleased” with the company’s plan, but noted that she hopes the HIV population will be included in clinical trials.

“I hope that the studies can be carried out in time because we need this information quite urgently,” said Carvalho.