The Pfizer study was stopped early for efficacy and the company plans to submit data to the US FDA for Emergency Use Authorization as soon as possible, according to a statement.
An oral investigational antiviral agent developed by Pfizer reduced by 89% the risk of hospitalization or death in non-hospitalized high-risk adults with COVID-19, according to a Pfizer company statement issued today.
A scheduled interim analysis of the randomized double-blind phase 2/3 EPIC-HR trial (N=1219) found that the combination of novel protease inhibitor PF-07321332 with HIV agent ritonavir (Paxlovid) vs placebo, reduced the need for inpatient treatment or death from any cause in adults treated within 3 days of COVID-19 symptom onset. Less than 1% (0.8%) of patients treated with the antiviral combination required hospitalization or died after 28 days of follow-up compared to 7% of those who received placebo, according to the statement (p<.001).
Findings were similar for patients treated within 5 days of becoming ill, with 1% of patients receiving PF-07321332/ritonavir requiring hospitalization vs 6% of placebo-treated patients.
There were no deaths reported through day 28 among patients treated with the novel antiviral combination according to the report, but there were 10 deaths in the placebo arm. Study enrollment was halted based on the positive interim findings and Pfizer plans to submit the data to the US Food and Drug Administration as soon as possible for potential Emergency Use Authorization.
The news released today is a "game changer,” says Pfizer chairman and CEO Albert Bourla. "These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections, and eliminate up to nine out of ten hospitalizations.”
Oral by design
The investigational SARS-CoV-2 protease inhibitor antiviral was designed specifically for oral administration, the company states, to ensure it can be prescribed when symptoms first appear or as soon as an individual is aware of exposure. The specific combination used relies on the ability of ritonavir to slow PF-07321332 metabolism, allowing the latter to remain active for longer periods at higher concentrations. PF-07321332/ritonavir dosing in EPIC-HR trial was oral administration every 12 hours for 5 days.
Safety analysis included 1881 patients and found treatment-emergent adverse events (AEs) mild and comparable between PF-07321332/ritonavir and placebo (19%, 21%). There were fewer serious AEs and study discontinuations in the treatment vs placebo group, according to Pfizer.
The company states that in preclinical studies PF-07321332 was not associated with evidence of mutagenic DNA interactions.
When the decision was made to end trial recruitment, enrollment was at 70% of the planned 3000 participants at clinical sites throughout the world, with 45% located in the US.
The Pfizer announcement comes just one day after the UK Medicines and Healthcare products Regulatory Agency approved Merk and Ridgeback's oral antiviral molnupiravir for the same indication. The approval, the first of a COVID-19 antiviral worldwide, was based on findings from the MOVe-OUT trial that showed a significant 50% reduction in risk of hospitalization or death vs placebo, reducing the rate from 14% to 7%.