Relief Therapeutics and NeuroRx expand clinical trial of RLF-100 to all patients with critical Covid-19 and respiratory failure

“With the FDA’s expanded definition of Critical COVID-19 to include patients on all forms of ventilation and the recent trend at leading hospitals that avoids mechanical ventilators whenever possible for patients with COVID-19, we recognized the potential benefit of extending this clinical trial to patients on newer forms of treatment for respiratory failure,” said Dr. Jonathan C. Javitt, MD, MPH, NeuroRx’s CEO and the National Study Chair.

Dr. Javitt continued: “The SARS-CoV-2 attacks the body by entering the small population of Alveolar Type II cells in the lung, almost like hitting the needle in the haystack.1 Without Type II cells, the lung cannot transmit oxygen, which is exactly what happens in COVID-19. We know, from 50 years of scientific research that VIP binds specifically to the Type II cell and protects that cell against cytokines (inflammatory molecules) and a wide array of toxic and infectious injuries.2”

The multicenter clinical trial will enroll patients with Critical COVID-19 and respiratory failure in the hopes that RLF-100 can decrease mortality and improve blood oxygenation in this condition by rescuing alveolar type II cells from the SARS-CoV-2 virus.

“In recent months, there has been significant focus on “cytokine storm” as a mechanism of death in COVID-19 and on the use of various anti-inflammatory drugs to block cytokines,” said Dr. Javitt. “While cytokine storm is certainly a consequence of the corona virus infecting the Type-II alveolar cells, we are hopeful that a more targeted approach to blocking the effects of the Corona Virus may stop the cytokine storm at an earlier stage.”

The trial is being led by NeuroRx, Inc., the US development partner of Relief Therapeutics, whose clinical operations are based in Radnor, PA. Patients are being treated under FDA Investigational New Drug clearance, as part of the FDA’s Corona Treatment Acceleration Program (CTAP).

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 II 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. Corona Viruses are shown to replicate in alveolar type 2 cells, but not in the more numerous type 1 cells. ² 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.

RLF-100 (Aviptadil) is a patented formulation of Vasoactive Intestinal Polypeptide (VIP) that was developed based on Dr. Said’s original work and was originally approved for human trials by the FDA in 2001 and the European Medicines Agency in 2005. VIP is known to be highly concentrated in the lungs 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 licenses for human trials of Aviptadil.

Source: Company Press Release