Interim phase II/III results suggest 89% redux in Covid-related hospitalization, death vs placebo

Pfizer Inc. announced that its investigational oral antiviral drug combo for Covid-19, PF-07321332/ritonavir (Paxlovid), significantly reduced rates of hospitalization or death compared to placebo among a cohort of non-hospitalized, high-risk adults with Covid-19.

According to early results from the randomized, double-blind, phase II/III Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients (EPIC-HR) trial, which have yet to be peer-reviewed, patients who received the novel treatment saw an 89% risk reduction for Covid-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset.

The manufacturer reported that “0.8% of patients who received Paxlovid were hospitalized through Day 28 following randomization (3/389 hospitalized with no deaths), compared to 7.0% of patients who received placebo and were hospitalized or died (27/385 hospitalized with 7 subsequent deaths). The statistical significance of these results was high (P<0.0001). Similar reductions in Covid-19-related hospitalization or death were observed in patients treated within five days of symptom onset; 1.0% of patients who received Paxlovid were hospitalized through Day 28 following randomization (6/607 hospitalized, with no deaths), compared to 6.7% of patients who received a placebo (41/612 hospitalized with 10 subsequent deaths), with high statistical significance (P<0.0001). In the overall study population through Day 28, no deaths were reported in patients who received Paxlovid as compared to 10 (1.6%) deaths in patients who received placebo.”

Adverse events were seen among 19% of patients in the intervention arm and 21% in the placebo arm, and most events were mild in intensity. The manufacturer’s press release did not clarify the side effects study participants experienced.

The company also announced that, on the recommendation of an independent data monitoring committee, it “will cease further enrollment into the study due to the overwhelming efficacy demonstrated in these results and plans to submit the data as part of its ongoing rolling submission to the U.S. FDA for Emergency Use Authorization (EUA) as soon as possible.”

The manufacturer described their new drug as “an investigational SARS-CoV-2 protease inhibitor antiviral therapy, specifically designed to be administered orally so that it can be prescribed at the first sign of infection or at first awareness of an exposure, potentially helping patients avoid severe illness which can lead to hospitalization and death. PF-07321332 is designed to block the activity of the SARS-CoV-2-3CL protease, an enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of PF-07321332 in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.”

The antiviral pill is the second such drug to demonstrate efficacy against Covid-19, with Pfizer’s announcement following a little less than a month after Merck and Ridgeback Biotherapeutics announced positive results for their own antiviral candidate, molnupiravir. The latter drug snagged its first approval yesterday from Britain’s Medicine and Healthcare products Regulatory Agency (MHRA), and the FDA’s Antimicrobial Drugs Advisory Committee is slated to meet on Nov. 30 to review data and vote on whether or not to authorize the drug for emergency use in the U.S.

While molnupiravir may be first up to bat for a chance at approval, Pfizer’s interim results seem superior to those for the other drug—molnupiravir only reduced the risk of Covid-19-related hospitalization or death by around 50%, compared to the 89% reduction for Pfizer’s pill. However, given the variable designs and timing between the two trials, it is difficult to say whether one drug will prove more effective than the other in the real-world setting.

The U.S. government has been negotiating a deal with Pfizer to procure enough pills for 1.7 million courses of the new treatment, a similar deal to the one it made with Merck earlier this year, the New York Times reported.

John McKenna, Associate Editor, BreakingMED™

Cat ID: 190

Topic ID: 79,190,730,933,190,926,192,927,151,928,925,934