Benzinga | Oct 14, 2021 06:50AM EDT

Journal of Infectious Diseases and Treatment Publishes Positive Trial Data of Aviptadil in High Comorbidity Patients Suffering from Critical COVID-19 with Respiratory Failure

NRx Pharmaceuticals (NASDAQ:NRXP), today announced the publication of peer-reviewed results from a prospective, open-label, administratively controlled trial of aviptadil for the treatment of respiratory failure in patients with Critical COVID-19. The study reported 60-day survival in 81% of those treated with aviptadil, compared to 21% survival among those who received standard of care treatment at the Houston Methodist Hospital (P<.0001). A similar 9-fold advantage was seen in the cumulative probability of recovery from respiratory failure (P<.0001). The study appears in the Journal of Infectious Diseases and Treatment.

"We view this study as supportive evidence that aviptadil protects the lung against the lethal effects of the SARS-CoV-2 virus," said Jihad Georges Youssef, M.D., Lead Author of the study.

Patients enrolled in this study were at the highest possible risk for death based on serious comorbidities that rendered them ineligible for participation in the phase 2b/3 pivotal study of aviptadil for the treatment of COVID-19 with respiratory failure. In addition, patients in the study failed to respond to all treatments approved for COVID-19 during the first surge of the pandemic in the summer of 2020.

In addition to the substantial differences seen for both survival and recovery, the study demonstrated statistically significant advantages in the aviptadil-treated group on two important intermediate endpoints: Respiratory Distress Ratio and Cytokine IL-6. Statistically significant differences on these endpoints have previously been noted in reports from the phase 2b/3 randomized controlled trial of aviptadil vs. placebo conducted at 10 sites across the United States. Aviptadil-treated participants in this open-label study demonstrated a rapid (48-96 hour) 2-fold improvement in the Respiratory Distress Ratio (RDR- a measure of the lung's ability to transmit oxygen to the blood), whereas no short-term improvement was seen in patients who were treated with standard of care (P<0001). A 100% reduction in cytokine IL-6 was also seen in aviptadil-treated patients (along with changes in other cytokines). It was not possible to compare the cytokine reduction to standard of care-treated participants because of the low survival in this control group.

"Although randomized, placebo-controlled trials are the gold standard for medical evidence, the findings in this open-label study are remarkably similar to those seen at tertiary care medical centers in the phase 2b/3 trial of aviptadil vs. placebo. Therefore, we view this study as supportive evidence that aviptadil protects the lung against the lethal effects of the SARS-CoV-2 virus," said Jihad Georges Youssef, M.D., Medical Director of Advanced Lung Diseases Program at Houston Methodist J. C. Walter Jr. Transplant Center and lead author on the study. "The patients enrolled in this trial had no therapeutic alternatives and 80% of those treated with standard of care died within 60 days of hospital admission. The corresponding improvement in RDR and cytokine levels add biologic plausibility to the findings. We believe these add important perspective to the potential for aviptadil to help some of the sickest patients with Critical COVID-19 recover and return home to their families."

The primary endpoint was survival as measured by Kaplan Meier life table, with Recovery from Respiratory Failure, World Health Organization 10-point ordinal scale, and PaO2: FiO2 ratio while on a ventilator as secondary endpoints. As required in the CONSORT description, no additional resources were added or removed from the usual care setting other than treatment or non-treatment with aviptadil.

The study team enrolled Standard of Care patients between May 23 and August 15, 2020, in intensive care units (ICU) of the Houston Methodist Hospital System, in Houston, Texas. All patients enrolled in the trial had Critical COVID-19 with respiratory failure. All patients in the study were treated by the same ICU team (regardless of admitting team) and received maximally available therapy, which included steroids, anti-coagulants, remdesivir, and, in some cases, convalescent plasma, with the test group receiving aviptadil.

No unexpected drug-related Serious Adverse Events (SAEs) were recorded. Hypotension was seen in two patients that were successfully managed, and treatment with aviptadil was continued. Diarrhea was observed in 4 aviptadil-treated patients, compared to 3 control patients (19% vs. 10%; p=0.2). These adverse events are congruent with those seen in the Phase 2b/3 randomized clinical trial of aviptadil in Critical COVID-19 patients.