New data suggest that inhalation of nitric oxide (NO) may improve lung function and alleviate the burden of serious lung infections, such as Mycobacterium abscessus complex (MABSC) and Pseudomonas aeruginosa, two serious pathogens affecting cystic fibrosis (CF) patients.
Results from the Advanced Inhalation Therapies (AIT) pilot study were shared recently at the 2018 American Thoracic Society (ATS) Conference in San Diego, California. The presentation was titled, “Nitric Oxide Inhalations in CF Patients Infected with Mycobacterium Abscessus Complex: A Prospective, Open-Labeled Multi-Center Pilot Study.”
“The data presented demonstrate the promise of NO for the treatment of patients with MABSC as well as Pseudomonas aeruginosa infections,” Steven Lisi, chairman and CEO of AIT Therapeutics, said in a press release.
In the study, a Phase 2 clinical trial (NCT03208764), nine CF patients (five females and four males) with non-tuberculous lung infection caused by MABSC were treated with NO. MABSC is the most aggressive and difficult-to-treat species of non-tuberculous mycobacteria.
Patients received 160 parts per million (ppm) of NO, delivered in 30-minute sessions, five times a day, for 14 days, followed by three sessions, daily for seven more days. NO administration was added on top of standard antibiotic therapy.
Patients were followed for 60 days after NO therapy sessions.
The trial’s main objective was to assess the NO’s inhalation safety and tolerability. Secondary goals included parameters assessing the therapy’s effectiveness: measurements of lung function (forced expiratory volume in one second (FEV1) and 6-minute walk distance (6MWD) tests), and; the bacterial load in the lungs of MABSC and other relevant pathogens, such as Pseudomonas aeruginosa. Patients’ quality of life also was assessed.
NO treatment was free of serious side effects, but was linked to hemoptysis (spitting of blood that originates in the lungs) and methemoglobin (MetHb), a form of hemoglobin that is unable to transport oxygen. But these two negative effects resolved quickly, not affecting patients, or only to a minor degree.
Treatment with NO resulted in an increase in 6MWD, reaching a mean increase of 44.8 meters (48 yards) from the beginning of the study at week 2 of treatment. The increase was still detected through weeks 4 and 8 after patients stopped the treatment.
Patients’ FEV1 also showed improvements, although modest, reaching a 4.1 percent increase at week 3 relative to the start of the study. The improvements were not noticeable 60 days after the treatment was stopped.
Infection by M. abscessus was completely cleared in one patient, and five of the nine patients showed a slight decrease in bacteria load by week 11. Of four patients co-infected with the multi-drug resistant P. aeruginosa, two of them bacteria were cleared, in another patient the load was reduced, and the fourth patient showed no change in bacterial load.
“The results of this study confirm the benefits of nitric oxide for patients suffering from MABSC and provide a glimpse into the potential for nitric oxide to benefit patients with other severe bacterial infections,” said Andrew Colin, MD, director, division of Pediatric Pulmonology at the University of Miami, and the principal clinical consultant of the study.
“I, along with patients, look forward to seeing a confirmatory study in the very near future,” Colin said.
Lea Bentur, MD, director of the Pediatric Pulmonary Institute at Rambam Health Care Campus and the trial’s principal investigator, added: “The benefits to the patient are real and meaningful, with an overall benign safety profile. Treating at a higher concentration of nitric oxide for a longer period of time in the patient’s home would be a very significant advancement in the care of these patients.”
AIT Therapeutics plans to pursue regulatory approval from the U.S. Food and Drug Administration (FDA).
“We will meet with the FDA later this quarter to discuss the path forward towards regulatory approval. With our generator-based NO delivery system we endeavor to treat patients in their homes for chronic, severe, refractory bacterial lung infections and hopefully improve upon the results just shown,” Lisi said.