Aries Pharmaceuticals’ AIR001 is a drug that is being developed by Mast Therapeutics for the treatment of heart failure with preserved ejection fraction (HFpEF). It is a sodium nitrite solution for intermittent inhalation via a nebulizer. Nitrite is a vasodilator and can be transformed in cells to form nitric oxide (NO). This has beneficial effects in patients by dilating their blood vessels, reducing inflammation, and slowing the growth of undesirable cells.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder that mostly affects lungs. It is characterized by persistent lung infections due to mucus obstruction in the airways, which allows bacteria to grow.

How does AIR001 work?

Pseudomonas aeruginosa is the most common bacterial infection found in the lungs of people with CF. Chronic airway infections can lead to cycles of airway inflammation that ultimately end in respiratory failure. Once P. aeruginosa is in the lungs, it is difficult to get rid of because its resistance mechanisms, including growth in biofilms.

Research by Anna Zemke and others showed that nitrite prevents 99 percent of biofilm formation by inhibiting P. aeruginosa growth in primary CF airway cells at concentrations compatible with AIR001. This finding led researchers to believe that AIR001 could be a novel therapy for chronic P. aeruginosa infections in conditions such as cystic fibrosis and non-CF bronchiectasis.

AIR001 studies for CF

In March 2017, the University of Pittsburgh agreed to conduct a clinical trial of AIR001 for the treatment of P. aeruginosa bacteria infections in patients with cystic fibrosis.

According to a press release, the University of Pittsburgh and Aries Pharmaceuticals (a subsidiary of Mast Therapeutics) entered into an agreement to conduct the trial. While researchers at Pitt will explore the effect of AIR001 on lung function, exhaled airway nitric oxide and bacterial density, Aries will provide AIR001 and nebulizers (the drug delivery devices) but will not otherwise support the study financially.

The study will consist of a Phase 1 and 2 open-label and proof-of-concept trial. The study’s aim will be to determine the safety of AIR001 administered in a dose escalation manner. It will enroll people with CF and P. aeruginosa airway infection.

Under the agreement, Aries will be able to use data and study results for potential regulatory submissions.

Other details

AIR001 was originally developed for the treatment of heart failure with a preserved ejection fraction (HFpEF), where three Phase 2 studies are currently recruiting participants.

The INABLE study (NCT02713126) is a single-center, randomized, interventional trial that aims to evaluate whether AIR001 improves the clinical responses and tolerability of exercise training in people with HFpEF.

Another Phase 2 trial known as the INDIE-HFpEF study (NCT02742129) aims to evaluate the effect of AIR001 on aerobic capacity after four weeks.

Another Phase 2 trial (NCT01431313) will evaluate the effect of two different doses of AIR001 (45 mg and 90 mg) on the change in pulmonary vascular resistance (PVR) in participants with pulmonary hypertension (PH) undergoing right heart catheterization. Initial results of this study, published in November 2016, showed that the drug is safe and well tolerated, and that it significantly lowers pulmonary, right atrial, and pulmonary capillary wedge pressures, most pronounced in patients with PH-HFpEF.

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