Mallinckrodt and Novoteris Receive Clearance from Health Canada to Start Pilot Trial of High-Dose Inhaled Nitric Oxide Therapy for COVID-19 Infection and Associated Lung Complications

Written by: Pharmiweb editor
Published on: 8 Apr 2020

-- Study to investigate antiviral activity and improvement in oxygenation and pulmonary arterial pressure in patients suffering from COVID-19 --

STAINES-UPON-THAMES, United Kingdom and GARDEN GROVE, Calif., April 1, 2020 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a global biopharmaceutical company, and Novoteris, LLC, a clinical stage medical device and pharmaceutical developer focused on innovative nitric oxide gas applications, today announced that the Therapeutic Products Directorate of Health Canada has cleared the companies' joint pilot clinical trial, entitled "Inhaled Gaseous Nitric Oxide (gNO) Antimicrobial Treatment of Difficult Bacterial and Viral Lung (COVID-19) Infections" application to investigate the use of Thiolanox®, a high-dose inhaled nitric oxide therapy for the treatment of patients infected with novel coronavirus (SARS-CoV-2) at Vancouver Coastal Health Authority facilities. The investigative therapy employs Novoteris' Inhaled Nitric Oxide Delivery Device (INODD) and Mallinckrodt's high-concentration, 5000 PPM nitric oxide gas for inhalation canisters. The study will investigate the therapy's safety and effectiveness in treating COVID-19 and its associated lung complications. The companies expect to begin recruiting patients in the coming days.

"Inhaled nitric oxide may have an antiviral effect, as well as improve oxygenation and pulmonary arterial pressure in patients suffering from COVID-19," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. "We're proud to be partnering with Novoteris on this pilot trial and are committed to increasing understanding of this potentially important therapeutic option for healthcare providers on the front lines of this unprecedented health emergency."

COVID-19 is a contagious respiratory illness caused by a novel coronavirus. Patients with COVID-19 have mild to severe respiratory illness that can include symptoms such as cough, fever and shortness of breath.1 In severe cases, COVID-19 can cause acute respiratory distress syndrome (ARDS) – a disorder in which fluid leaks into the lungs, making breathing difficult or impossible – and can lead to multi-organ failure and sometimes death.1,2

"Our collaboration with Mallinckrodt to study high-dose inhaled nitric oxide to treat patients with COVID-19 and associated lung complications is an exciting step in both companies' commitment to helping the world battle this global pandemic," said Alex Stenzler, Founder and President at Novoteris.

Inhaled nitric oxide (iNO) has been evaluated in randomized controlled trials, both in pediatric and adult patients with ARDS,3,4,5,6,7 and demonstrated partially dose-dependent improvement in blood oxygenation and decreased pulmonary artery pressure3 and, in one trial, improvements in the composite measure of days alive or free of ventilator support at day 28 of the trial (the last day evaluated).8 There have been other trials evaluating iNO in the context of ARDS, which have demonstrated mixed results.6,7,9 In an in vitro study, inhaled nitric oxide has demonstrated an inhibitory effect on the replication cycle of severe acute respiratory syndrome-related coronavirus (SARS-CoV).10 Furthermore, a small clinical trial in SARS-CoV patients demonstrated improvements in blood oxygenation, a reduction in supplemental oxygen and a reduction in the amount of ventilator support.11

"This is an important day for patients and healthcare providers," said Chris Miller, Ph.D., Assistant Professor, Faculty of Medicine at University of British Columbia and Founder and Scientific Advisor at Novoteris.  Dr. Miller, team lead for the study at Vancouver Coastal Health Research Institute, and an expert in nitric oxide therapies, with a research career spanning more than 25 years studying the antimicrobial effect of high-dose nitric oxide to treat lung infections, said, "I am very pleased to be working with Mallinckrodt and Novoteris on this study using high-dose inhaled nitric oxide for patients with COVID-19."

Mallinckrodt is currently working with the U.S. Food and Drug Administration on the possibility of making the company's INOmax® (nitric oxide) gas, for inhalation product available to U.S. patients with pulmonary complications of COVID-19 as quickly as possible through the appropriate regulatory mechanism.  INOmax has been on the market in the U.S. since 2000, and is indicated for the treatment of term and near-term neonates with hypoxic respiratory failure associated with pulmonary hypertension. Please see Important Safety Information below. The safety and efficacy of INOmax and iNO for pulmonary complications associated with COVID-19 have not been established. 

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