Pfizer announced its investigational novel COVID-19 oral antiviral candidate, PAXLOVID, significantly reduced hospitalization and death, based on an interim analysis of the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High Risk Patients) randomized, double blind study of non hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness.
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The scheduled interim analysis showed an 89% reduction in risk of COVID-19 related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint); 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.
At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. Food and Drug Administration (FDA), Pfizer 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.
“Today’s news is a real game changer in the global efforts to halt the devastation of this pandemic. 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,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer.
“Given the continued global impact of COVID-19, we have remained laser-focused on the science and fulfilling our responsibility to help healthcare systems and institutions around the world while ensuring equitable and broad access to people everywhere.”
If approved or authorized, PAXLOVID, which originated in Pfizer’s laboratories, would be the first oral antiviral of its kind, a specifically designed SARS-CoV-2-3CL protease inhibitor.
Upon successful completion of the remainder of the EPIC clinical development program and subject to approval or authorization, it could be prescribed more broadly as an at home treatment to help reduce illness severity, hospitalizations, and deaths, as well as 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 its potential as a therapeutic for multiple types of coronavirus infections.
The Phase 2 3 EPIC-HR study began enrollment in July 2021. The Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) and EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) studies, which began in August and September 2021 respectively, were not included in this interim analysis and are ongoing.
PAXLOVID isan 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.
PF-07321332 inhibits viral replication at a stage known as proteolysis, which occurs before viral RNA replication. In preclinical studies, PF-07321332 did not demonstrate evidence of mutagenic DNA interactions.
Pfizer initiated the EPIC-HR study in July 2021 following positive Phase 1 clinical trial results and continues to evaluate the investigational antiviral in additional EPIC studies.
In August 2021, Pfizer initiated the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients), to evaluate efficacy and safety in patients with a confirmed diagnosis of SARS-CoV-2 infection who are at standard risk (i.e., low risk of hospitalization or death).
EPIC-SR includes a cohort of vaccinated patients who have an acute breakthrough symptomatic COVID-19 infection and who have risk factors for severe illness. In September, Pfizer initiated the Phase 2 3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) to evaluate efficacy and safety in adults exposed to SARS-CoV-2 by a household member. ■