Another investigational new drug application (IND) was submitted with the U.S. Food and Drug Administration’s Coronavirus Treatment Acceleration Program (CTAP) to conduct a Phase II/III clinical trial investigating inhaled RLF-100 as a treatment for patients with non-acute lung injury caused by SARS-CoV-2, the virus behind the COVID-19 pandemic. A patented formulation of Aviptadil, RLF-100 is a synthetic human vasoactive intestinal polypeptide (VIP)—known in animal models to inhibit inflammatory cytokines and to protect pulmonary epithelial cells that line the air sacs (alveolae) of the lung. NeuroRX Inc., the U.S. partner of Swiss-based Relief Therapeutics Holding AG (SIX:RLF) submitted the IND and hopes to commence clinical trials soon.
The Medical Challenge Associate with COVID-19
According to the joint press release from Relief Therapeutics and NeuroRx, findings suggest that the type-2 alveolar cells are particularly vulnerable to SARS-CoV-2 because of cell surface receptors that allow the virus to enter the cell. The type-2 cells are essential to replenishing the pulmonary epithelium and to manufacturing surfactant, which coats the inside of the lung and allows oxygen exchange to occur. Without surfactant, the alveolae fails to remain open and blood oxygen rapidly drops as is the case in COVID-19 patients.
The Assumption Behind Drug Need
Those patients infected with COVID-19 induced non-acute lung injury who have demonstrated reduction in blood oxygenation, dyspnea and exercise intolerance but don’t need endotracheal intubation and mechanical ventilation will be treated with RLF-100 (Aviptadil).
The drug: Enter RLF-100
The sponsors of RLF-100 have identified the potential for this experimental drug to help save lives. Already in clinical trials for the treatment of Acute Respiratory Distress Syndrome (ARDS) in COVID-19 patients on mechanical ventilation, four out of five patients who progress to this acute, severe stage of COVID-19 disease are reported to die regardless of the fact that they are treated in maximum intensive care.
What is the background of RLF-100 AKA Aviptadil?
RLF-100 is a patented formulation of Vasoactive Intestinal Polypeptide (VIP) that was originally developed and is currently marketed in Europe for the treatment of erectile dysfunction. VIP is known to be highly concentrated in the lung and to inhibit a variety of inflammatory cytokines. Relief’s predecessor company, Mondo Biotech, was awarded Orphan Drug Designation in 2001 by the U.S. FDA for Aviptadil in the treatment of Acute Respiratory Distress Syndrome and in 2005 for treatment of pulmonary arterial hypertension. Mondo was awarded Orphan Drug Designation by the European Medicines Agency in 2006 for the treatment of acute lung injury and in 2007 for the treatment of sarcoidosis. Both the U.S. FDA and the EMEA have granted Investigational New Drug (IND) licenses for human trials of Aviptadil.
The study will treat patients with RLF-100 plus standard of care versus placebo and standard of care. The Patients will be randomized to intravenous Aviptadil will receive inhaled Aviptadil, 100 ug 3x daily versus placebo 3x daily. The sponsor identified the primary outcome as progression to ARDS over 28 days. Secondary outcomes include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance and levels of TNFα IL-6 and other cytokines.
The multicenter randomized, placebo-controlled trial will target 144 patients with COVID-19 for enrollment—they must be experiencing shortness of breath and early pulmonary symptoms in an effort to slow COVID-19 progression. As these patients can still breath on their own, RLF-100 will be inhaled. Inhaled dosing supports delivery of RFL-100 directly to the lung tissue most at risk from the novel coronavirus.
The sponsor is targeting 20 sites although they do not list the sites in Clinicaltrials.gov.
About the Sponsors
The Relief group of companies, including RELIEF THERAPEUTICS focus primarily on clinical-stage projects based on molecules of natural origin (peptides and proteins) with a history of clinical testing and use in human patients or a strong scientific rational. Currently, Relief is concentrating its efforts on developing new treatments for respiratory disease indications.
NeuroRx, Inc. is a clinical stage pharmaceutical company that is developing NRX-101, the first oral therapeutic for the treatment of Acute Suicidal Behavior/Ideation (ASIB) in Bipolar Disorder.