Inhaled nitric oxide for the treatment of COVID-19 and other viral pneumonias in adults

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.

NITRIC OXIDE IS A POWERFUL ANTI-CORONAVIRUS-INHALED AGENT THAT ACTS WITHIN HOURS

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Nitric oxide (NO) is a small endogenous messenger molecule with free radical characteristics that plays a key role in the pathophysiological processes in the lung, including host defense against airway pathogens. NO donors have been reported to inhibit replication of severe acute respiratory syndrome coronavirus (SARS-CoV-1) in vitro, and exogenous gaseous NO (gNO) at concentrations = 150ppm has been shown to act as a potent antimicrobial agent. In multiple clinical trials, administration of high dose (150 to 250ppm) intermittent gNO (30-40 min cycles, 2-5 cycles a day) was safe and well-tolerated, with promising antimicrobial efficacy potential. Beyond Air™ has developed the LungFit™ platform system, which produces and delivers up to 400 ppm gNO from ambient air to the human lung, eliminating the need for cylinders. Given its safety and antimicrobial activity, inhaled gNO is a potential treatment for patients with COVID-19. The objective of this in vitro study is to evaluate the use of gNO as a method of treating human coronavirus infection as a proof of concept for the treatment of SARS-CoV-2. METHODS: OC43 human coronavirus was exposed to 150-250ppm gNO, for up to 8 hours intermittently (1-hour alternating) both before and after infection of human HCT-8 cells. Host cell viability was assessed by an XTT cell proliferation-based assay 3-7 days post exposure to NO. The coronavirus viability was assessed by TCID50 (Median Tissue Culture Infectious Dose) 3-7 days post exposure. RESULTS: When coronavirus was exposed to 250ppm NO prior to infection, a significant reduction in infectivity was achieved as viral load was reduced by 24-fold compared to untreated sample and host cell viability was higher by more than 85% (p<0.05). Post infection exposure of OC43 coronavirus to 250ppm NO resulted in 45% increase in host cell viability (p<0.05). Upon exposure of coronavirus infected cells to 150ppm NO. While coronavirus lost 50% of its infectivity after 4 hours of treatment with 150ppm NO, complete inhibition of infectivity was achieved after 8 hours of treatment. CONCLUSIONS: These results indicate the potential of inhaled gNO as a novel treatment for COVID-19. According to our data, 150-250ppm gaseous NO shows anti-coronavirus properties against OC43 human coronavirus in vitro, when administered either prior to or post infection. CLINICAL IMPLICATIONS: The data presented shows that the use of NO and the LungFit™ system may be effective for usage in both prevention and treatment of the SARS-CoV-2 infection. DISCLOSURES: No relevant relationships by Amir Avniel, source=Web Response No relevant relationships Added 07/15/2020 by Hila Confino, source=Web Response, value=Salary Removed 07/15/2020 by Hila Confino, source=Web Response No relevant relationships Added 07/15/2020 by Hila Confino, source=Web Response, value=Salary Removed 07/16/2020 by Hila Confino, source=Web Response No relevant relationships Added 07/15/2020 by Elya Dekel, source=Web Response, value=Salary Removed 07/16/2020 by Elya Dekel, source=Web Response No relevant relationships by Pam Golden, source=Web Response No relevant relationships Added 07/15/2020 by Matan Goldshtein, source=Web Response, value=Salary Removed 07/16/2020 by Matan Goldshtein, source=Web Response Owner/Founder relationship with Beyond air company Please note: $20001 - $100000 Added 06/11/2020 by David Greenberg, source=Web Response, value=Consulting fee No relevant relationships Added 05/26/2020 by Rinat Kalaora, source=Web Response, value=Salary Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 05/26/2020 by Rinat Kalaora, source=Web Response, value=stocks Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/16/2020 by Rinat Kalaora, source=Web Response, value=Salary Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/16/2020 by Rinat Kalaora, source=Web Response, value=Shares Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/15/2020 by Omer Lerner, source=Web Response, value=Salary Removed 07/16/2020 by Omer Lerner, source=Web Response No relevant relationships by Steve Lisi, source=Web Response No relevant relationships by Yonat Shemer-Avni, source=Web Response No relevant relationships Added 07/16/2020 by Shay Yarkoni, source=Web Response, value=Salary Removed 07/16/2020 by Shay Yarkoni, source=Web Response No relevant relationships Added 07/16/2020 by Shay Yarkoni, source=Web Response, value=Shares Removed 07/16/2020 by Shay Yarkoni, source=Web Response