NeuroRx Announces ZYESAMI Trial Met Primary Endpoint

NeuroRx reports 60-day results of the Phase 2b/3 trial of intravenously-administered ZYESAMI™ (aviptadil acetate) for the treatment of respiratory failure in critically-ill patients with COVID-19, which is being developed in collaboration with Relief Therapeutics Holding. Across all patients and sites, ZYESAMI™ met the primary endpoint for successful recovery from respiratory failure at days 28 (P = .014) and 60 (P = .013) and also demonstrated a meaningful benefit in survival (P = < .001) after controlling for ventilation status and treatment site.

In addition to the robust overall significance across all 196 treated patients at all 10 clinical sites, the prespecified analysis of recovery from respiratory failure is clinically and statistically significant in the 127 patients treated by High Flow Nasal Cannula (HFNC) (P = .02), compared to those treated with mechanical or non-invasive ventilation at tertiary care hospitals. In this group, ZYESAMI™ patients had a 71% chance of successful recovery by day 28 vs. 48% in the placebo group (P = .017) and a 75% rate of successful recovery by day 60 vs. 55% in the placebo group (P = .036). Eighty-four percent (84%) of HFNC patients treated at tertiary medical centers with ZYESAMI™ survived to day 60 compared with 60% of those treated with placebo (P = .007).

To the company's knowledge, ZYESAMI™ is the first COVID-19 therapeutic to demonstrate advantages in both survival and recovery from critical COVID-19 in a randomized, double-blind multicenter trial. On the basis of these findings, NeuroRx plans to apply immediately to the United States Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) and to subsequently submit a New Drug Application (NDA).

Recovery from respiratory failure (without relapse) with discharge from acute care and survival through the observation period was the prespecified primary endpoint specified by FDA for the study, originally intended to be assessed at 28 days and then extended to 60 days based on recently-published FDA guidance. The above analysis includes all 196 participants who were randomized and treated in the placebo-controlled, double-blind clinical trial conducted at 10 US hospitals. Treatment with ZYESAMI™ or placebo was in addition to standard of care treatment that included steroids, convalescent plasma, antiviral therapy, anticoagulants, and various anti-cytokine drugs.

NeuroRx has announced the commencement of a clinical trial of inhaled ZYESAMI™ for the treatment of patients with moderate and severe COVID-19 with the aim of preventing progression to respiratory failure. NeuroRx has also announced the inclusion of inhaled ZYESAMI™ in the I-SPY clinical trial platform for patients with COVID-19 respiratory failure. The company has signed a clinical trial participation agreement with the National Institutes of Health.

"ZYESAMI has now demonstrated itself in a phase 2/3 trial, conducted under FDA Fast Track Designation, not only to shorten hospitalization (as was previously reported) but also to save lives and increase the likelihood of patients returning safely home to their families. In exactly 12 months, a lifesaving drug has advanced from concept to clinical success in partnership with Relief Therapeutics in the midst of a public health emergency that has claimed the lives of millions. Today's findings confirm the often dramatic clinical success that has been seen in numerous patients treated in the US and abroad under emergency use protocols. We look forward to working with the National Institutes of Health, the Department of Defense, the FDA, and regulators around the world to bring this treatment to patients as quickly as possible," Prof. Jonathan Javitt, MD, MPH, Chairman and CEO of NeuroRx, said.