Pfizer’s Paxlovid Could Deliver Knockout Blow to COVID

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Pharmaceutical giant Pfizer announced today that Paxlovid, its investigational novel COVID oral antiviral candidate, significantly reduced hospitalisation and death, based on an interim analysis of its phase II/III clinical trials showing an 89% reduction of risk of hospitalisation or death due to COVID. 

The phase II/III EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomised, double-blind study of non-hospitalised adult patients with COVID, who are at high risk of progressing to severe illness. The scheduled interim analysis showed an 89% reduction in risk of COVID-related hospitalisation or all-cause mortality compared to placebo in patients treated within three days of symptom onset (primary endpoint). Only 0.8% of patients who received Paxlovid were hospitalised through Day 28 with zero deaths, compared to 7.0% of patients who received placebo and were hospitalised or died. Similar reductions in COVID-related hospitalisation or mortality were seen in patients treated within five days of symptom onset; 1.0% of patients in the intervention arm were hospitalised through Day 28 with zero deaths, compared to 6.7% of placebo arm patients. In the overall study population through Day 28, no deaths were reported in intervention arm patients as compared to 10 (1.6%) deaths in placebo arm patients.

The results show such an overwhelming effectiveness that Pfizer, in consultation with the US Food and Drug Administration (FDA), will cease further enrollment into the study and will apply for Emergency Use Authorization (EUA) as soon as possible.

If it gets the green light, Pfizer’s Paxlovid, would be the first oral antiviral of its kind, a specifically designed SARS-CoV-2-3CL protease inhibitor. PF-07321332 inhibits viral replication at the proteolysis stage, before viral RNA replication. Co-administration with a low dose of ritonavir helps slow the metabolism of PF-07321332 in order for it to remain active in the body for longer at higher concentrations. It has shown effectiveness against multiple variants, and could have broad general effectiveness against coronaviruses.

“All of us at Pfizer are incredibly proud of our scientists, who designed and developed this molecule, working with the utmost urgency to help lessen the impact of this devastating disease on patients and their communities,” said Mikael Dolsten, MD, PhD, Chief Scientific Officer and President, Worldwide Research, Development and Medical of Pfizer. “We’re thankful to all of the patients, investigators, and sites around the world who participated in this clinical trial, all with the common goal of bringing forth a breakthrough oral therapy to help combat COVID.”

The review of safety data included a larger cohort of 1881 patients in EPIC-HR, whose data were available at the time of the analysis. Adverse events were comparable between paxlovid (19%) and placebo (21%), which were mostly mild.

Pfizer kicked off the EPIC-HR study in July 2021 after positive results from Phase I clinical trials, followed in August by the Phase II/III 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 (low) risk. This trial includes a cohort of vaccinated at-risk patients who have an acute breakthrough COVID infection. A further trial is investigating prophylaxis among household members of patients with a COVID infection. 

Source: Pfizer