Pfizer Says Patients Who Relapse After Covid Pill Can Repeat

(Bloomberg) -- Pfizer Inc. executives said patients who suffer a relapse in Covid-19 symptoms after taking a full course of Paxlovid should take more of the treatment, though current U.S. guidelines limit use to five consecutive days.

“Paxlovid does what it has to do: it reduces the viral load,” Chief Executive Officer Albert Bourla said in an interview. “Then your body is supposed to do the job.” But for unknown reasons, the CEO said, some patients aren't able to clear the virus with the first course of treatment.

In cases where virus levels do rebound, Bourla said, “then you give a second course, like you do with antibiotics, and that's it.”

The Food and Drug Administration didn't immediately respond to a request for comment on how the antiviral should be prescribed to Covid-19 patients who experience the rebound in viral load. While Paxlovid is available under emergency use authorization, it hasn't yet gained full approval. Prescribing directions suggest that the drug is “not authorized for use for longer than 5 consecutive days.”

President Joe Biden has made Paxlovid a key feature of his pandemic strategy, and a National Institute of Allergy and Infectious Diseases scientist said it's critical to understand why virus levels rebound in certain patients who have completed a five-day course treatment. The Centers for Disease Control and Prevention is also providing data to help study the phenomenon, according to an email.

Bourla and other top executives say they're taking the matter seriously, though they believe the phenomenon is rare and unrelated to the drug. A clinical trial of high-risk patients showed that about 2% who received Paxlovid experienced viral load rebound, according to the executives.

The rate of rebound was about the same among patients who received placebo, suggesting that the drug was likely not responsible for the resurgence, they said. Pfizer said it has found no link between certain patient characteristics and the recurrence of severe symptoms after finishing the treatment.

“This is more about the virus and the disease in certain patients than a characteristic of Paxlovid,” Chief Scientific Officer Mikael Dolsten said. The drugmaker is looking at causes that might include the existence of reservoirs of virus in tissues or cells that aren't reached by treatment, or the possibility that patients may become reinfected, he said.

Pfizer said Tuesday that Paxlovid sold $1.5 billion in the first quarter, missing analysts' $2.4 billion estimate, with the vast majority of revenue coming from the U.S. The company left unchanged its annual forecast for $22 billion in 2022 global sales of the pill. The shares rose 2.5% as of 3:17 p.m. in New York after falling 18% this year through Monday's close.

The New York-based drugmaker aims to launch a new study in the second half of the year of Paxlovid in Covid patients with compromised immune systems. These patients have a more difficult time clearing infections, and the study will look to extend the duration of treatment to help them clear the virus.

Another Course

Doctors contacted by Bloomberg have reported seeing numerous patients with the viral rebound phenomenon in recent weeks.

David Wohl, a professor at the Institute of Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill, has already run into difficulty getting a second course of Paxlovid to a high-risk patient whose symptoms returned after treatment. The patient was denied a repeat course of Paxlovid after her pharmacy submitted the request for the second round of treatment, he said.

The pharmacy was able to get around this block by resubmitting the request for Paxlovid as if it were an entirely new infection, Wohl said, rather than treating it as an extension of the original bout of Covid.

“Pfizer's statement fails to recognize the reality of use of the drug,” under emergency-use authorization, Wohl said.

Paul Sax, a Harvard Medical School professor at Brigham and Women's Hospital in Boston, said that while prescribing instructions aren't clear at the moment, the Mass General Brigham health system is developing guidance on the issue for clinicians in case that the FDA allows for repeat treatment.

“Clearly this is most important for patients who are severely immunocompromised, or otherwise quite fragile medically,” Sax said.

Viral Debate

Top virus experts have argued that Paxlovid might indirectly contribute to the rebound phenomenon.

“I'm very concerned” about the rebound cases, former Harvard epidemiologist Michael Mina wrote in a series of tweets. It could occur when rapid initiation of treatment results in the immune system not activating the way it otherwise would have, he said. “This may call for an 8- or 10-day course of treatment rather than 5 days.”

Drugs like Paxlovid help shut down actively replicating virus, Yale University immunologist Akiko Iwasaki said, which also shuts down production of viral proteins the immune system responds to.

“If you start treating the patients very early during the infection, they may not generate much of an immune response to the virus,” Iwasaki said in an email. If the virus starts to rebound after Paxlovid is gone, there may not be much of an immediate immune response to counteract it, she said.

Ashley Brown, a virologist at the University of Florida in Orlando, said that longer dosing might help if the problem is caused by unusually high viral load in some people, or occurs mostly in immune compromised people who have trouble clearing the virus. But another possibility is that the rebounds are occurring because the virus sometimes persists in a part in the body the drug is unable to get to. If that is the case, then longer treatment regimens might not help, she said.

Right now, “there are not a lot of answers,” said Brown. “It is another one of these weird curve-balls the virus is throwing at us.”