Novel Oral Antiviral Treatment Reduced Risk of COVID-19 Hospitalization, Death by 89% in Phase 2/3 Study

If authorized, ritonavir could be prescribed broadly as an at-home treatment to help reduce COVID-19 severity, hospitalizations, and deaths, as well as to reduce the probability of infection following exposure among adults.

A novel oral antiviral treatment for COVID-19 from Pfizer showed significant reductions in the risk of hospitalization or death in an interim analysis of the phase 2/3 EPIC-HR study, according to a press release.

Ritonavir (Paxlovid) is an investigational novel COVID-19 oral antiviral candidate that is being investigated in the randomized, double-blind EPIC-HR study. If authorized, ritonavir could be prescribed broadly as an at-home treatment to help reduce COVID-19 severity, hospitalizations, and deaths, as well as to reduce the probability of infection following exposure among adults. It has demonstrated potent antiviral in vitro activity against circulating variants of concern as well as other known coronaviruses, suggesting it could be efficacious for multiple types of infections.

“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 9 out of 10 hospitalizations,” said Albert Bourla, DVM, PhD, chairman and CEO of Pfizer, in the press release.

Participants in the EPIC-HR study were non-hospitalized adults with COVID-19 who are at high risk of progressing to severe illness. According to the press release, the scheduled interim analysis found an 89% reduction in the risk of COVID-19-related hospitalization or death from any cause compared to placebo among patients who were treated within 3 days of symptom onset. Just 0.8% of patients who received ritonavir were hospitalized through day 28 following randomization, compared to 7% of patients in the placebo arm who were hospitalized or died.

These results also had a high statistical significance, with similar reductions in COVID-19-related hospitalization or death observed among patients treated within 5 days of symptom onset. Among patients who received ritonavir within 5 days, 1% were hospitalized through day 28 following randomization, compared to 6.7% of patients who received a placebo. In the overall study population through day 28, no deaths were reported in the ritonavir arm compared to 10 deaths in the placebo arm.

Based on these encouraging efficacy results, with the recommendation of an independent data monitoring committee, and in consultation with the FDA, Pfizer will cease further study enrollment. The company plans to submit the data for emergency use authorization as soon as possible.

The phase 2/3 EPIC-HR study began enrollment in July 2021, and other studies are ongoing to investigate protease inhibition for COVID-19 in patients with standard risk levels, as well as for post-exposure prophylaxis. At the time of decision to halt recruitment, enrollment was at 70% of the 3000 planned patients for the EPIC-HR study.

The review of safety data included a larger cohort of 1881 patients whose data were available at the time of the analysis. Treatment-emergent adverse events (AEs) were comparable between ritonavir and placebo, at 19% and 21%, respectively. Among patients evaluable for treatment-emergent AEs, fewer serious AEs (1.7% and 6.6%, respectively) and discontinuation of study drug due to AEs (2.1% and 4.1%, respectively) were observed in patients dosed with ritonavir compared to placebo.

REFERENCE

Pfizer’s novel COVID-19 oral antiviral treatment candidate reduced risk of hospitalization or death by 89% in interim analysis of phase 2/3 EPIC-HR study. News release. Pfizer; November 5, 2021. Accessed November 5, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate