Pfizer reported today final results of the phase 2/3 EPIC-HR trial, findings that confirm the investigational drug's 89% efficacy against severe COVID-19 disease.
Pfizer’s investigational COVID-19 oral antiviral agent Paxlovid (nirmatrelvir [PF-07321332] tablets and ritonavir tablets) retained efficacy of 89% at reducing the risk of hospitalization and death in full findings of a phase 2/3 study of more than 2000 high-risk patients, the company announced on Tuesday in a press statement.
The results, the company said, were consistent with those from an interim analysis reported in November which also showed that the antiviral significantly reduced risk of hospitalization and death for any cause by 89% vs placebo in the high-risk population when patients were treated within 3 days of symptom onset. In the current analysis, when administered within 5 days of appearance of symptoms, Paxlovid efficacy was nearly the same at 88%, an increase from 85% seen in the interim analysis.
Pfizer has submitted the data to the US Food and Drug Administration (FDA) as the next step in an ongoing rolling submission for Emergency Use Authorization (EUA).
“This news provides further corroboration that our oral antiviral candidate, if authorized or approved, could have a meaningful impact on the lives of many, as the data further support the efficacy of Paxlovid in reducing hospitalization and death and show a substantial decrease in viral load,” said Pfizer chairman and CEO Albert Bourla in the statement. He adds that the evolution of SARS-CoV-2 variants, including Delta and Omicron, have made the need for effective and accessible treatments more urgent than ever and says, “we are confident that, if authorized or approved, this potential treatment could be a critical tool to help quell the pandemic.”
The phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) study enrolled 2,246 patients at high-risk of serious illness (ie, required to have at least one underlying medical condition that placed them at increased risk of severe illness from COVID-19). Patients were randomized 1:1 to receive oral Paxlovid or placebo every 12 hours for 5 days.
In final analysis of the EPIC-HR primary endpoint, the company reports, <1% (0.7%) of patients who received Paxlovid within 3 days of experiencing symptoms were admitted to hospital through study day 28 vs 6.5% of those who received placebo and were hospitalized or died (p<.001); 9 deaths were reported in the placebo group, according to Pfizer.
Similar results were seen on analysis of a key secondary endpoint. In patients treated within 5 days of symptom onset, 0.8% of Paxlovid-treated patients were hospitalized or died through day 28 after randomization compared to 6.3% of those who received placebo (p<.001). Pfizer notes in the press release that there were 12 deaths among those who received placebo 5 days after experiencing symptoms.
Among participants aged ≥65 years, considered to be at high risk, the relative risk reduction was 94%; 1.1% of patients in this group who received Paxlovid were hospitalized through day 28 compared to 16.3% of patients who received placebo (p<.001).
Importantly, in evaluation of a separate secondary endpoint, SARS-CoV-2 viral load at baseline and day 5, after multivariable adjustment, Paxlovid reduced viral load by approximately 10-fold relative to placebo, an outcome that Pfizer claims is the strongest viral load reduction so far reported for an oral COVID-19 agent.
Adverse events (AEs) were similar between Paxlovid (23%) and placebo (24%), Pfizer reports, and the majority were mild in intensity. Fewer serious AEs (1.6% vs 6.6%) and discontinuations related to study drug AEs (2.1% vs 4.2%) occurred in Paxlovid- vs placebo-treated patients, respectively.
There was no information made available on racial and cultural diversity of the study population and those who were pregnant or breastfeeding were excluded from the trials.
The pill would be available for patients soon after an FDA approval, CEO Bourla told CNBC in an interview. “We have already shipped product into the US, so product will be available this month if it’s approved.”
President Biden said last month the US has already purchased 10 million courses of Paxlovid and that delivery will be feasible by the end of the years, according to the CNBC report.