Inhaled Nitric Oxide for the Treatment of COVID-19 and Other Viral Pneumonias in Adults

Abstract

RATIONALE: There is a growing population at increased risk of viral pneumonia;over 50,000 people in the United States died from pneumonia in 2015. RSV, influenza, and other viruses are common causes of severe viral lower respiratory tract infection (LRTI), and COVID-19 pneumonia is associated with high mortality rates. With limited treatment options currently available, viral COVID-19 LRTI in particular represents a significant unmet medical need. Inhaled nitric oxide (iNO) is a highly promising treatment option, given its documented antimicrobial and anti-inflammatory effects as well as beneficial effects on pulmonary vasculature. In particular, the antiviral effect of iNO on SARS-CoV-2 has been attributed to covalent binding to SARS-CoV-2 protease. In multiple clinical trials and compassionate use cases, intermittent exposure to 150 - 250 ppm iNO was well tolerated, resulted in improved physical and lung function, reduced bacterial load in patients with cystic fibrosis , and shortened time to improvement of clinical signs and time to fit for discharge in patients with acute bronchiolitis. Based on these data, we have initiated a prospective, randomized, open label, multi-center pilot clinical trial to evaluate the safety and efficacy of iNO for the treatment of viral pneumonia in adult patients. METHODS: In the current study, subjects (ages 18-80) with COVID-19 (COVID group) or other acute viral pneumonias (Viral LRTI group) requiring inpatient hospitalization are being randomized 1:1 to be treated with intermittent inhalations of 150 ppm iNO, given for 40 minutes 4 times daily for up to 7 days in addition to standard supportive treatment (SST), or to receive SST alone. iNO is being delivered by the LungFitTM, an innovative portable device under development (Beyond Air, NY, USA) that generates NO from room air. Study endpoints include safety, ICU admission, O2 supplementation requirement, and time to resolution of fever. RESULTS: The study will be conducted in up to 10 centers in Israel. To date, 6 subjects have been enrolled (COVID group), three have been randomized to iNO + SST and three to SST alone. All treatments have been well tolerated. CONCLUSIONS: Based on current data demonstrating the antiviral and anti-inflammatory effects of NO, in addition to its complex beneficial effect on oxygenation, iNO delivered by the LungFit system has the potential to treat viral pneumonias including COVID-19, thereby providing therapy for this currently unmet medical need.