Paxlovid's post-exposure protection flop hardly spells the end for Pfizer's COVID franchise: analysts

Heavy is the head that wears the COVID-19 crown. Late last week, Pfizer revealed its antiviral Paxlovid fell short in a post-exposure protection trial. Still, in the pill’s quest to reach as many patients as possible, one setback doesn’t spell defeat.

Top-line results from the phase 2/3 EPIC-PEP study showed a five- and 10-day Paxlovid course curbed the risk of infection by 32% and 37%, respectively, versus placebo, in adults exposed to the virus through someone they live with. The readout fell short of statistical significance, the company said late Friday.

Safety looked good in EPIC-PEP whether patients took Paxlovid for five or 10 days, Pfizer said in a release. It’s wrapping up secondary endpoints and subgroup analyses for the study’s full data drop, expected in the "coming months."

“We designed the clinical development program for Paxlovid to be comprehensive and ambitious with the aim of being able to help combat COVID-19 in a very broad population of patients,” Albert Bourla, Ph.D., Pfizer’s CEO, said in a statement.

“While we are disappointed in the outcome of this particular study, these results do not impact the strong efficacy and safety data we’ve observed in our earlier trial for the treatment of COVID-19 patients at high risk of developing severe illness, and we are pleased to see the growing global use of Paxlovid in that population.”

Pfizer’s prophylaxis trial weighed data from 2,957 patients who tested negative for the virus and didn’t have any symptoms. For study inclusion, participants had to have been exposed to a symptomatic household contact with COVID-19 within the last four days.

In the study—which started recruitment in September and wrapped up “during the peak of the COVID-19 Omicron wave,” Pfizer said—patients received Paxlovid or placebo twice daily for either five or ten days.

Paxlovid’s post-exposure protection flop “does not change our view that the peak sales potential of [Pfizer’s] COVID-19 franchise (vaccine and oral antiviral) is still under-appreciated,” Cantor Fitzgerald analysts wrote in a note to clients, calling the results a “bump in the road.”

Because Pfizer’s clinical development for Paxlovid is “comprehensive and ambitious,” not “every trial needs to work for the drug to be successful,” the Cantor team said.

SVB Securities analysts mostly agreed, saying they “remain optimistic that the treatment setting alone offers a large market opportunity for multiple players” with next-gen protease inhibitor (PI) oral antivirals. They added the caveat that the Pfizer readout could have “incrementally negative readthrough” for the class in the protection setting, however.

Still, it would be “premature to entirely write off the prophylaxis opportunity for next-gen PI antivirals based on the (minimal) EPIC-PEP data so far," the SVB team said.

PI antivirals’ outpatient treatment prospects remain bright, the SVB Securities analysts continued. The “silver lining,” as they put it, “is that the efficacy bar for next-gen oral antivirals in post-exposure prophylaxis of COVID-19 is now quite low."

Other PI contenders include Enanta Pharmaceuticals and Pardes Biosciences. Those companies have an opportunity to learn from Pfizer’s trial and show protection benefit with their PI antivirals, “perhaps by focusing on incidence of hospitalizations/deaths and by treating high-risk individuals,” SVB said.

Merck’s Paxlovid rival molnupiravir, for its part, has a post-exposure protection trial that’s expected to finish in late August and read out sometime later this year, Cantor Fitzgerald added.

Some other unknowns that could play in Paxlovid’s favor are its late-stage trial in standard risk non-hospitalized COVID-19 patients—expected to read out the second half of the year—and sales opportunities in Europe and China, the analysts said.

Outside the clinic, Paxlovid is at a curious crossroads. While demand for the drug has lagged, according to anecdotal reports, the U.S. government has stepped in with a 20-million-course order and a pledge to boost manufacturing and supply of the pill. 

Nevertheless, the company currently expects Paxlovid to generate full-year sales of roughly $22 billion. Pfizer plans to report first-quarter earnings this week.