NeuroRx, Inc. and Relief Therapeutics Holdings AG announced that as of today, 150 patients (out of a targeted enrollment of 165) have been enrolled in the ongoing phase 2b/3 trial of RLF-100™ (aviptadil) for treating respiratory failure in patients with Critical COVID-19. Respiratory failure is defined, according to FDA guidance, as the need for intensive care with mechanical ventilation, non-invasive ventilation, or high-flow nasal oxygen in order to sustain adequate levels of blood oxygen. So far, no drug-related Serious Adverse Events have been reported.
There is currently no FDA-approved drug that has shown efficacy in patients who are already in the Intensive Care Unit (ICU) with Respiratory Failure. Although NeuroRx and Relief are optimistic that RLF-100™ will also be effective in treating early COVID-19, the companies have focused first on those patients who have no available therapy and are at the highest risk of mortality. An open-label prospective study in patients with Critical COVID-19 has already shown a nine-fold hazard ratio advantage in both survival and recovery from respiratory failure with both statistically significant (P < .001). More than 110 patients with similar severity have additionally been treated nationwide under an FDA-sanctioned Expanded Access Protocol (NCT04453839).
Although the phase 2b/3 study remains blinded, illustrative blinded recoveries from signs of Critical COVID-19 on Chest x-ray within 10 days have been reported by study sites and shared with the study's Data Monitoring Committee and FDA (see figure). Until the study is unblinded, it cannot be known whether this rapid recovery was more frequent among patients treated with RLF-100™ compared to those treated with placebo. However, in the open-label prospective study, more rapid recovery was seen among 21 patients treated with RLF-100TM than those treated with standard of care with an average of nine fewer ICU days in the RLF-100TM treated patients compared to those treated with Standard of Care.
Completion of enrollment is anticipated in the coming weeks. Enrollment was uniquely challenged by the devastating effects of the pandemic. It strained the capacity of hospitals and caused the temporary incapacity of investigators and study coordinators at several study sites, who themselves contracted COVID-19 in the course of their duties.
"Should RLF-100™ prove to be safe and effective for treating COVID-19 Respiratory Failure, the nation will owe an eternal debt of gratitude to the front-line healthcare workers, technicians, study coordinators, nurses, and doctors who worked seven days a week to help develop this treatment while risking their own health to do so. They are the true heroes," said Prof. Jonathan Javitt, CEO and founder of NeuroRx, Inc.
About VIP in Lung Injury
Vasoactive Intestinal Polypeptide (VIP) was first discovered by the late Dr. Sami Said in 1970. Although first identified in the intestinal tract, VIP is now known to be produced throughout the body and to be primarily concentrated in the lungs. VIP has been shown in more than 100 peer-reviewed studies to have potent anti-inflammatory/anti-cytokine activity in animal models of respiratory distress, acute lung injury, and inflammation. Most importantly, 70% of the VIP in the body is bound to a rare cell in the lung, the alveolar type 2 cell, that is critical to transmission of oxygen to the body. VIP has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, pulmonary fibrosis, asthma/allergy, and pulmonary hypertension.
COVID-19-related death is primarily caused by respiratory failure. Before this acute phase, however, there is evidence of early viral infection of the alveolar type 2 cells. These cells are known to have angiotensin converting enzyme 2 (ACE2) receptors at high levels, which serve as the route of entry for the SARS-CoV-2 into the cells. Coronaviruses are shown to replicate in alveolar type 2 cells but not in the more numerous type 1 cells. These same type 2 alveolar cells have high concentrations of VIP receptors on their cell surfaces giving rise to the hypothesis that VIP could specifically protect these cells from injury.
Injury to the type 2 alveolar cells is an increasingly plausible mechanism of COVID-19 disease progression (Mason 2020). These specialized cells replenish th...
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