Add Pfizer to the long list of victims of ACTIV-3. While the Big Pharma has enjoyed unparalleled success in COVID-19, it was unable to buck the trend in the National Institutes of Health (NIH) study of hospitalized patients and has stopped development of Paxlovid’s intravenous sibling PF-07304814.
The NIH set up ACTIV-3 to test anti-SARS-CoV-2 monoclonal antibodies and other therapies in patients hospitalized with COVID-19. Brii Biosciences, Eli Lilly, GlaxoSmithKline and Novartis are among the drug developers to contribute candidates to the study. All those candidates failed to move the needle in hospitalized patients with severe COVID-19, resulting in a persistent unmet need even as the broader pandemic armory has gone from strength to strength.
PF-07304814 represented a different answer to the question of how to treat severe COVID-19. Like one of the components of Pfizer’s oral COVID-19 drug Paxlovid, PF-07304814 is a SARS-CoV-2 main protease inhibitor. The idea was to expand into patients with severe COVID-19 through intravenous delivery.
That plan, like others tested by Pfizer’s peers, came unstuck in NIH’s ACTIV-3 trial. Dosing of the intravenous antiviral in the trial has stopped, and Pfizer has discontinued the global clinical development. Pfizer said the decision “was made based on a totality of information, including a careful review of early data and a thorough assessment of the candidate’s potential to successfully fulfill patient needs.”
The discontinuation means ACTIV-3 is no longer enrolling patients. In a recent update to the listing on ClinicalTrials.gov, the sponsor changed the status from “recruiting” to “active, not recruiting” and added “Suspended: Participants are not currently being randomized to this intervention” to the description of the PF-07304814 arm. Patients aren’t being randomized into any of the other arms, either.
ACTIV-3 has been a rare graveyard for COVID-19 programs. The global vaccine race and push to create therapies for mild to moderate COVID-19 each featured multiple successes. But efforts to improve on Gilead Sciences' Veklury in hospitalized COVID-19 patients have floundered, potentially because by that point in the disease pathway elements other than the virus are at play. The NIH is still pushing ahead, though.
"The ACTIV-3 program has not ended. The ACTIV-3 inpatient protocol is no longer enrolling participants to receive PF-07304814. However, ACTIV-3b, also known as the ACTIV-3 critical care protocol, continues to randomize participants to receive aviptadil. Looking ahead, ACTIV-3 partners are considering ways to evolve to evaluate different treatment strategies based on different stages of disease," a spokesperson for the National Institute of Allergy and Infectious Diseases said.
Pfizer disclosed the discontinuation of PF-07304814 in its quarterly pipeline update. The Big Pharma also used the update to reveal the end of work on PRMT5 inhibitor PF-06939999 in solid tumor patients and PF-07059013 in sickle cell disease. Both programs were in phase 1.
Editor's note: This story was updated at 05:10 a.m. ET on Feb. 9 to include information from the NIAID.