NRx Pharmaceuticals announced it has filed an application with U.S. Food and Drug Administration (FDA) requesting Emergency Use Authorization (EUA) for ZYESAMI (Aviptadil-acetate), to treat Critically Ill COVID-19 patients suffering with respiratory failure. Consistent with previously announced top-line data, the study identified a statistically significant increase in the likelihood that patients treated with ZYESAMI™ would be alive and free of respiratory failure at 60 days, compared to those treated with placebo, and identified a significantly shorter median hospital stay. The clinical study report filed with FDA further documents statistically significant advantages for ZYESAMI on all major secondary endpoints.
“The patients enrolled in our study were in the ICU, having exhausted all approved treatments for COVID-19,” said Jonathan Javitt, M.D, MPH, Chief Executive Officer and Chairman of the Board, of NRx. “We look forward to working as quickly as possible with the FDA in hopes of providing critically ill patients with a new medicine that will increase their chances of recovery and survival, enabling them to leave the hospital and return to their families significantly sooner.”
Patients enrolled in the study had respiratory failure despite prior treatment with all approved medicines for COVID-19 including remdesivir. Other therapies administered included steroids, anticoagulants, and various monoclonal antibodies. Although antiviral treatment has shown advantages in treating patients with earlier stages of COVID-19. ZYESAMI is the first reported medicine to demonstrate increased recovery and survival in patients who have already progressed to respiratory failure. The randomized controlled trial outcomes remain similarly consistent with the open-label, administratively controlled trial reported in October 2020.
“Since this pandemic started, there have been very few medications to effectively treat COVID-19,” said Dushyantha Jayaweera, MD, Professor of Clinical Medicine and former Associate Dean, University of Miami, who served as Principal Investigator for the COVID-AIV trial. “The positive results from this trial turned into positive implications for some of our sickest COVID-19 patients and support the clinical benefit of ZYESAMI™ in critically-ill COVID-19 patients with respiratory failure. Even today, despite the availability of vaccines, we continue to see severely ill patients suffering with COVID-19, who desperately need new medicines to help them recover.”
The study enrolled one hundred ninety-six participants who were randomized and treated with either ZYESAMI™ or placebo, in addition to maximal standard of care at 10 US hospitals (www.clinicaltrials.gov NCT04311697). Patients in earlier stages of respiratory failure (those treated with high flow oxygen) were more likely to survive and recover than those who had already progressed to ventilation. However, statistically-significant benefits in the prespecified endpoint were demonstrated in both groups.
NRx previously requested limited EUA for highly co-morbid COVID-19 patients. FDA further requested randomized, prospective data regarding ZYESAMI, which are represented in this filing.
Separately, the National Institutes of Health is conducting a confirmatory trial that randomizes patients with COVID-19 respiratory failure to ZYESAMI vs. Veklury (remdesivir) and placebo in a factorial design trial (clinicaltrials.gov NCT04843761). A second nationwide trial to determine if similar benefits may be achieved in critically ill patients with inhaled ZYESAMI is being conducted on the I-SPY platform, maintained by the Quantum Leap Healthcare Collaborative.
The COVID-AIV clinical trial was co-funded by NRx and Relief Therapeutics Holding, AG. The clinical study report has been shared with Relief Therapeutics for transmission to European health regulatory authorities.