Data Promising on Nitric Oxide as Treatment Against Mycobacterium abscessus, AIT Reports

Inhaled nitric oxide, AIT Therapeutics’ therapy candidate, was shown to have significant antibacterial activity against the bacterium Mycobacterium abscessus (M. abscessus), which often infects the airways of patients with cystic fibrosis.

AIT announced the results of a laboratory study in a poster presentation titled, “High-dose Nitric Oxide as an Antibacterial Agent Against Mycobacterium abscessus,” at the European Respiratory Society International Congress 2018 held recently in Paris.

In the airways of the lungs, nitric oxide (NO) is thought to be an important part of the immune system. Laboratory studies have suggested that NO is an effective therapeutic against not only against common bacteria but also other microorganisms such as mycobacteria, fungi, yeast, and parasites. It also has the potential to be effective against multidrug-resistant strains.

AIT set out to evaluate the use of high-dose NO as an antibacterial therapeutic in the treatment of Mycobacterium abscessus complex (MABSC), which comprises a group of rapidly growing, multidrug-resistant species of nontuberculous mycobacteria.

Many patients with MABSC have an underlying respiratory disease, such as cystic fibrosis or chronic obstructive pulmonary disease (COPD).

Currently, there are no approved treatments for MABSC, and the standard-of-care is based on a cocktail of antibiotics that is often ineffective and carries serious adverse effects.

AIT therefore investigated in vitro the sensitivity of several multidrug-resistant clinical isolates of M. abscessus to NO, which was delivered at specific concentrations using a custom-designed NO delivery system.

M. abscessus was cultured in artificial sputum (a mixture of saliva and mucus) to mimic the sputum of cystic fibrosis patients. The sputum was then treated with humidified medical air or high-dose NO, at a concentration of 160-400 ppm, for up to 10 hours.

Results indicated that there was significant dose-dependent antibacterial activity of high-dose NO against numerous multidrug-resistant clinical isolates of M. abscessus.

In addition to results presented on the treatment of MABSC, AIT also presented promising results on the use of inhaled NO in children with bronchiolitis.

“We look forward to initiating a pivotal trial [for the treatment of bronchiolitis] in the fourth quarter of calendar year 2019 with a premarket approval (PMA) submission to FDA anticipated to take place in the second half of 2020. In addition, we presented in vitro data that further demonstrates the potential of nitric oxide as a monotherapy to treat Mycobacterium abscessus lung infection, the most aggressive and difficult to treat species of non-tuberculous mycobacteria (NTM),” Steven Lisi, chairman and CEO of AIT Therapeutics, said in a press release.