NeuroRx announced results from its phase 2b/3 trial for its investigational therapy, aviptadil, in patients with severe COVID-19.
Patients with severe COVID-19 dealing with respiratory failure can have extended hospital stays and experience higher mortality rates. As such, an urgent need to aid these patients in respiratory failure is a priority in COVID-19 clinical care.
COVID-19-related respiratory failure is caused by selective infection of the alveolar type II cell (ATII) by the SARS-CoV-2 virus. The ATII cells are vulnerable because of their (ACE2) surface receptors, which serve as the route of entry for the virus. These specialized cells manufacture surfactant that coats the lung and is essential for oxygen exchange. Loss of surfactant causes collapse of the air sacs (alveolae) in the lung and results in respiratory failure.
Biopharmaceutical company, NeuroRx, in collaboration with Relief Therapeutics, have developed aviptadil, previously known as RLF-100, (Zyesami), a therapy targeting the lungs for patients in COVID-19 respiratory distress. Aviptadil contains a vasoactive intestinal polypeptide (VIP), a natural occurring peptide in the body that has been shown to protect the lungs from SARS-CoV-2. VIP has shown to block coronavirus replication in the ATII cell, block cytokine synthesis, block viral-induced cell death (cytopathy), and upregulate surfactant production.
Aviptadil is being studied in 2 clinical trials looking at intravenous and inhaled administration. Last week, NeuroRx announced results from its phase 2b/3 trial for aviptadil for the treatment of respiratory failure in critically ill COVID-19 patients.The company reports the investigational therapy demonstrated multidimensional benefit around its primary endpoint of recovery from respiratory failure with discharge from hospital and ICU (without relapse) by day 28 in patients with critical COVID-19 who were treated with high flow nasal oxygen.
Although not envisioned at the start of this clinical trial, high flow nasal oxygen has become the predominant form of treatment in COVID-19 respiratory failure, with mechanical ventilation reserved for those whose blood oxygen levels cannot be maintained on this less invasive modality.
“We started off giving it [aviptadil] to the people who were critically ill with COVID-19—people who were on ventilators, high-flow oxygen. And we are now just starting studies where it will be given in an inhaled form for people who are less sick,” NeuroRx CEO and Chairman Jonathan Javitt, MD, MPH, told Contagion. “Most pulmonary drugs are best given in inhaled form but once someone has COVID distress and is on a ventilator there is a lot of debris in the lungs and reasons to give it intravenously.”
The first trial was originally approved as a 28-day study. However, in December, NeuroRx added a 60-day endpoint based on the recognition that critically ill patients with COVID-19 are frequently maintained in the ICU with advanced technologies beyond this time.
Nonetheless, at 28 days, the trial did demonstrate positive results. The cohort of patients treated with aviptadil demonstrated a 35% higher likelihood of recovery from respiratory failure with continued survival compared to a patient group treated with placebo (Hazard Ratio 1.53; P=.08). In tertiary care hospitals, aviptadil-treated patients were 46% more likely to recover and return home before day 28 (Hazard Ratio controlling for age and severity 1.84; P=.058).
At day 28, a highly significant 10-day difference in median time to recovery and hospital discharge has emerged in aviptadi-treated patients compared to those treated with placebo (P<.006). Should these trends continue through day 60, the company said they have the potential to reach statistical significance.
Contagion spoke to NeuroRx CEO and Chairman Jonathan Javitt, MD, MPH, about the significance of the Zyesami brand name, the therapy's mechanism of action, and the details about the 2 trials.