Mallinckrodt, Novoteris’ nitric oxide will start COVID-19 trial

Mallinckrodt and Novoteris have been given a green light by Health Canada to start a pilot study of an inhaled formulation of nitric oxide (NO) as a possible treatment for coronavirus.

The study will be carried out at Vancouver Coastal Health Authority facilities and will test a high-concentration form of NO called Thiolanox in development by the two companies, delivered using a specialised Novoteris delivery device. It is due to start recruiting patients in the next few days.

The UK-based drugmaker said in a statement that NO may have direct antiviral activity against SARS-CoV-2, the virus which causes COVID-19.

Furthermore, NO could also tackle the lung complications that afflict people who get seriously ill after infection by improving oxygenation of the lungs and pulmonary arterial pressure, according to Mallinckrodt.

Inhaled NO has already been tested in children and adults with acute respiratory distress syndrome (ARDS), a type of respiratory failure characterised by rapid and widespread inflammation in the lungs which can occur in severe COVID-19.

Admittedly, those studies yielded mixed results. On the plus side, inhaled NO has shown what appears to be dose-dependent  increases in blood oxygenation and decreased pressure in the pulmonary artery, and in one study improved the number of days ARDS patients were alive or didn’t need a ventilator.

There has however been a small trial in patients with SARS-CoV – which caused an earlier coronavirus outbreak – which also showed that the treatment improved blood oxygenation and reduced the need for oxygen masks and ventilator support.

The Canadian pilot study will use a higher concentration of NO than in the earlier trials, and will also deploy a delivery machine – the Inhaled Nitric Oxide Delivery Device (INODD) – specially designed to deliver Thiolanox in clinical trials.

Novoteris and Mallinckrodt have also been testing the NO system in diseases such as resistant bacterial and fungal lung infections in cystic fibrosis and non-tuberculous mycobacteria infections, based on the premise that gaseous NO has antimicrobial properties.

US trials planned

Meanwhile, Mallinckrodt has been talking to the FDA about filing for approval to start trials of its already-marketed INOmax NO product in patients with COVID-19.

The drug has been approved since 2000 to treat respiratory problems in newborn babies, and it is one of Mallinckrodt’s top brands, making $571 million in sales last year.

It’s facing generic competition from Praxair Technologies however, and lost an appeal in a patent litigation lawsuit last August, so is expected to see a decline in revenues in 2020.