RADNOR, Pa. and GENEVA, Nov. 5, 2020 /PRNewswire/ — NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTCBB:RLFTF) (“Relief”) announced that the independent Data Monitoring Committee (DMC) met yesterday and voted unanimously that NCT 04311697 should continue as planned to its full enrollment of 165 patients. Specifically, the committee identified no safety concerns and viewed the study as capable of reaching its prespecified endpoint (i.e. no finding of futility) in potentially proving that RLF-100™ (aviptadil) is superior to placebo in achieving recovery from Respiratory Failure in patients with Critical COVID-19 at a statistically significant level.
RLF-100™ was granted FDA Fast Track designation in June 2020 and was previously granted Orphan Drug Designation for the treatment of Acute Respiratory Distress Syndrome. In an earlier, open label study of patients with severe comorbidities that disqualified them from the randomized prospective trial, a statistically-significant (P<.0001) benefit in both recovery from respiratory failure and in survival was seen compared to control patients who received Standard of Care treatment (http://dx.doi.org/10.2139/
The review by the DMC was based on data from 102 patients who were randomly assigned to intravenous RLF-100™ vs. placebo and who have completed 28 days or more of observation. All patients were hospitalized in intensive care units with respiratory failure treated by mechanical ventilation, non-invasive ventilation, or high-flow nasal oxygen. So far, 133 patients have been treated in this protocol. At current rates of enrollment (which may change as infection rates change) the study is expected to complete enrollment by mid-December and yield top-line data in January 2021.
Although the study remains blinded, the randomized data overall show that there have been no drug-related Serious Adverse Events to date. Similarly, no drug-related adverse events were seen in either the open label study of the ongoing Expanded Access Protocol.
In contrast to other recently-reported trials, the RLF-100™ phase 2b/3 trial focuses on patients with Critical COVID-19 who already require intensive care for Respiratory Failure. Currently, there is no approved drug that has shown efficacy in this population, nor are there late stage trials of other experimental therapeutics focusing on these patients.
The seven-person DMC included two independent biostatisticians, an epidemiologist/clinical trials expert, a bioethicist, a public representative, and clinical experts in pulmonary and critical care medicine.
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-
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 the more common type 1 cells that line the lungs. More importantly, type 2 cells manufacture surfactant that coats the lung and are essential for oxygen exchange. Other than RLF-100™, no currently proposed treatments for COVID-19 specifically target these vulnerable type 2 cells.
Post courtesy of PRNewswire