Pfizer’s Oral COVID-19 Treatment Scores in Phase 2/3

April 20, 2022

Pfizer’s novel antiviral nirmatrelvir plus ritonavir cut the risk of COVID-19-related death or hospitalization by 89 percent relative to placebo, a phase 2/3 study has determined.

The safety analysis was also positive, Jennifer Hammond, wrote this week in the New England Journal of Medicine.

Nirmatrelvir targets an enzyme that SARS-CoV-2 needs for replication. In mouse studies, the drug has also shown benefit in other coronavirus infections. A low dose of co-administered ritonavir appears to enhance the action of nirmatrelvir, said Hammond, who leads Pfizer’s COVID-19 therapeutic global clinical and medicine team.

The combination was tested in the EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) trial. It enrolled 2,246 unvaccinated, nonhospitalized patients with symptomatic COVID-19 to either 300 mg of nirmatrelvir plus 100 mg of ritonavir or placebo every 12 hours for five days.

The primary endpoint was COVID-19–related hospitalization or death from any cause through day 28 in patients treated within three days of reporting symptoms. A secondary endpoint looked at these outcomes in patients who were treated within five days of becoming symptomatic.

A planned interim analysis comprised only the patients treated within three days of symptom onset. In this group, the drug combo reduced the composite endpoint of hospitalization or death by 89 percent; there were no deaths in the treated group, while seven died in the placebo group.

The final analysis upheld these results. Five patients in the treated group (0.72 percent) and 44 in the placebo group (6.45 percent) experienced the composite endpoint. This translated to an 88.9 percent risk reduction relative to placebo. No one in the treated group died, but there were nine deaths in the placebo group.

The drug was similarly effective in the subgroup of patients treated within five days of symptom onset, reducing the risk of the composite endpoint by 87.8 percent.

Among the most frequently reported adverse events in the treatment group were abnormal taste sensations (5.6 percent vs. 0.3 percent placebo); diarrhea (3.1 percent vs. 1.6 percent), and fibrin D-dimer increase (1.9 percent vs. 2.8 percent).

Nirmatrelvir appears far more effective than Merck’s molnupiravir, the only oral COVID-19 treatment with FDA Emergency Use Authorization for use in the high-risk, nonhospitalized population. Molnupiravir conferred a 30 percent risk reduction in COVID-19 hospitalization or death. It was approved in December (DID, Dec. 1, 2021).

Remdesivir is similarly effective, with an 87 percent risk reduction for progression to severe disease. However, Hammond noted, it’s an intravenous drug, while nirmatrelvir is an oral agent.

Read the full study here: bit.ly/3L1lxDG. — Michele G. Sullivan