Mast Therapeutics presented positive interim data from its Phase 2a clinical trial of the investigational drug AIR001 in patients with pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF). The condition for which no proven therapeutic agent is available, affects millions in the U.S.
Lead investigator Dr. Marc A. Simon showed the interim results in the poster “Efficacy and safety of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction.”
The ongoing open label Phase 2a clinical trial is evaluating the effect of AIR001, a sodium nitrite solution for intermittent inhalation via nebulizer, delivered in a dose escalation manner, on changes in cardiovascular hemodynamics in patients with PH who undergo standard right heart catheterization.
Results from the 10 patients studied to date demonstrated that the administration of AIR001 lowered central pressures; more specifically the right ventricular systolic and diastolic, right atrial, pulmonary artery (PA) systolic/diastolic/mean, and pulmonary artery occlusion (PAOP) pressures. Pulmonary artery occlusion and mean pulmonary artery pressures were significantly reduced compared to baseline values.
Additionally, the results showed an increase in pulmonary artery compliance, with no significant decline in systemic blood pressures or change in heart rate. There was also a modest increase in methemoglobin levels, but the levels remained less than 1.9 percent and did not meet the 5 percent discontinuing criteria of the study.
“This is the first report of the acute hemodynamic effects of multiple inhaled nitrite doses in patients with pulmonary hypertension due to heart failure with preserved ejection fraction,” said Simon in a press release. “The interim results observed to date are important as they demonstrate that AIR001 can significantly lower right atrial pressures, pulmonary artery pressures, and pulmonary artery occlusion pressures, as well as improve pulmonary artery compliance.”
Mast Therapeutics’ chief executive officer Brian M. Culley, said the data are consistent with results seen in a separate Phase 2a study of AIR001 in HFpEF earlier this year,
“And are a further step in validating our second asset and establishing the potential clinical utility of AIR001 in HFpEF,” Cully said. “We look forward to advancing AIR001 in this area of high unmet medical need for which there is no FDA-approved therapy available.”
AIR001 Inhalation Solution is sodium nitrite formulated with a phosphate buffer into an inhalation solution. Nitrite is a physiological signaling molecule with roles in intravascular endocrine nitric oxide (NO) production, hypoxic vasodilation, signaling, and cytoprotection after ischemia-reperfusion. Nitrite serves as the largest physiologic reservoir of NO, and can be converted to NO independent of NO synthase (NOS) activity.