Pfizer’s Combo COVID-19 Pill Reduced Risk of Hospitalization, Death

Pfizer’s investigational antiviral, Paxlovid (07321332 plus ritonavir) cut the risk of COVID-19 associated hospitalizations and death by 89 percent compared to placebo in an interim analysis of a phase 2/3 study, the company announced Friday.

So great was the impact that an independent Data Safety Monitoring Board stopped the study, “due to the overwhelming efficacy,” the company said. Pfizer will now ask the FDA to grant Paxlovid an Emergency Use Authorization (EUA) “as soon as possible,” according to Pfizer.

Pfizer’s oral antiviral for COVID-19 is likely to go head-to-head against Merck’s and Ridgeback Biotherapeutics’ oral COVID-19 medication, which got its first green light from a regulatory body last week when the UK approved it, making it the first oral antiviral medicine authorized for the treatment of COVID-19. The companies still await authorization from the FDA, which could come early next month.

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has authorized molnupiravir for the treatment of mild-to-moderate COVID-19 in adults who have at least one risk factor for developing severe illness.

The authorization triggers a procurement agreement under which Merck will supply 480,000 courses of the therapy to the UK government. And Merck has a separate agreement to supply approximately 1.7 million courses of molnupiravir to the U.S. government, once the FDA issues an EUA or approval.

The European Medicines Agency (EMA) has initiated a rolling review of the company’s marketing authorization application.

Pfizer’s Paxlovid is a dual-agent medication. It comprises a low dose of the antiviral ritonavir with Pfizer’s  novel protease inhibitor, PF-07321332, specifically designed to target SARS-CoV-2 proteins. It inhibits viral replication and has not shown DNA mutagenesis, the company said.

“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 infection, and eliminate up to nine out of 10 hospitalizations,” said Albert Bourla, Pfizer’s chairman and CEO.

When recruitment ceased, the EPIC-HR trial (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) had randomized 1,219 patients. The study cohort was quite heterogenous, drawing patients from North and South America, Europe, Africa and Asia. Patients had confirmed COVID-19 with mild-to-moderate symptoms and at least one underlying high-risk medical comorbidity. The cohort received Paxlovid or placebo every 12 hours for five days.

The interim analysis looked at two groups: patients treated within three days of symptom onset and patients treated within five days.

In the early-treatment group, the drug was associated with an 89 percent reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo.  Just 0.8 percent of patients in the active group (3/389) were hospitalized during the 28-day study period; there were no deaths. In the placebo group, 7 percent were hospitalized (27/385) and there were seven subsequent deaths.

The results were similar in the later-treatment group. Just 1 percent  in the active group were hospitalized (6/607); there were no deaths. In the placebo group, 6.7 percent were hospitalized (41/612) and there were 10 subsequent deaths.

The drug appeared safe and well-tolerated. Treatment-emergent adverse events  were similar in both Paxlovid and placebo groups (19 percent vs. 21 percent). Serious adverse events were more common in the placebo group (1.7 percent vs. 6.6 percent), as was discontinuation due to adverse event (2.1 percent vs. 4.1 percent). — Michele G. Sullivan