FDA Grants Inhaled Use IND for RLF-100 for COVID-19 to Prevent Respiratory Failure

NeuroRx and Relief Therapeutics announced NeuroRx has been granted Investigational New Drug (IND) permission to test RLF-100 (aviptadil) for inhaled use in patients with moderate and severe COVID-19 in order to prevent progression to respiratory failure.

The first phase will commence with patients hospitalized for severe COVID-19 who do not yet have respiratory failure. If promising results are seen in the inpatient setting, the trial will expand to patients at home with mild and moderate COVID-19 in order to prevent the need for hospital admission.

"Now that we know VIP suppresses replication of the SARS-CoV-2 virus in human lung cells, based on the outstanding work of the Oswaldo Cruz Institute (Rio de Janeiro),1 we are optimistic that treatment with VIP will not only help patients on ventilators, but will help to stop the advancement of the virus in patients with earlier stages of COVID-19. By blocking cytokine synthesis in the lung cells and increasing the production of surfactant, which is key to the lung's ability to transmit oxygen, we are hopeful that inhaled VIP will prove to be of clinical benefit across a wider array of patients suffering respiratory complications from COVID-19 infection," Professor Jonathan Javitt, MD, MPH, CEO of NeuroRx said.

The clinical trial of the inhaled formulation of RLF-100 is expected to begin on or before September 1, 2020.

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, which is critical for the 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 the more common type 1 cells that line the lungs. More importantly, type 2 cells manufacture surfactant that coats the lung and is 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 Mondo and Relief have worked on development of an inhaled formulation of aviptadil for several years. Both the U.S. FDA and the EMEA have granted Investigational New Drug licenses for human trials of aviptadil.