ZYESAMI, (aviptadil), being assessed by NRx Pharmaceuticals, failed a review conducted by the Data Safety and Monitoring Board (DSMB), with the board recommending that arm of the trial cease.
With the COVID-19 pandemic well into its third year, physicians have limited options to treat severely ill patients - and now they will have one fewer option. ZYESAMI, (aviptadil), being assessed by NRx Pharmaceuticals, failed a review conducted by the Data Safety and Monitoring Board (DSMB), with the board recommending that arm of the trial cease.
The ACTIV-3b trial began in April 2021 and was designed to determine the effectiveness of certain COVID-19 treatments. The National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), sponsored and managed the study.
The Phase III trial consisted of patients who were critically ill with COVID-19. In a control arm, patients received aviptadil, a corticosteroid, as a monotherapy and in combination versus placebo. It was tested against several other experimental combinations of drugs, including a combination of aviptadil and Gilead’s antiviral remdesivir.
The study’s primary endpoint was patient recovery, as measured by the need for supplemental oxygen. Patients were measured on a six-point scale from being at home with supplemental oxygen to the worst-case scenario of death.
As part of the study, the DSMB reviewed safety and efficacy data at least monthly. In the last review of the study on Wednesday, the DSMB measured 460 patients who were enrolled in the trial. Because around 75% of patients had already reached the end of the trial’s 90-day timeframe, the reviewers knew that the study was on track to miss its primary endpoint.
A secondary endpoint, patient mortality, was also concerning. The aviptadil group of patients experienced mortality rates of 37%, while the placebo group had a mortality rate of 36%.
The DSMB recommended the NIH stop the evaluation of aviptadil due to futility.
There were no safety concerns with aviptadil. Even though the drug did not prove effective in the treatment of critical COVID-19, the known side effects - diarrhea and hypotension - were well managed.
“We thank the NIH and the Trial Leadership for its extensive work in studying Zyesami® (aviptadil). We will continue to work closely with them to better understand the data over the coming months. This will also enable us to evaluate the options for Zyesami® in protecting the lung in other respiratory disorders, as well as its potential in other therapeutic areas,” said Robert Besthof, interim CEO of NRx Pharmaceuticals. “Critical COVID-19 remains a very high unmet need associated with significant mortality. “
Aviptadil is a synthetic form of human Vasoactive Intestinal Peptide (VIP), which reduces lung inflammation and protects alveolar type II cells, which are believed to be one way that SARS-CoV-2 enters the lungs.
In June 2020, aviptadil was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of respiratory distress in COVID-19. In 2001, the FDA gave avipdatil Orphan Drug Designation for the treatment of Acute Respiratory Distres Syndrome. In 2005, the FDA awarded it Orphan Drug Designation, this time for the treatment of pulmonary arterial hypertension.
After the disappointing news, NRx indicated it will focus its attention on another drug, NRX-101.
“Our corporate focus remains to apply innovative science to known molecules in order to address very high unmet needs. We have a flexible infrastructure that allows us to focus our resources on our Breakthrough Therapy designation drug NRX-101. We are already actively enrolling patients in our Phase II study for bipolar depression,” Besthof said.
