Use of INOpulse — inhaled nitric oxide — increased physical activity and improved patient-reported outcomes in people with pulmonary fibrosis (PF) who are at risk of pulmonary hypertension (PH), new topline clinical trial data suggest.
INOpulse, developed by Bellerophon Therapeutics, is a device that delivers nitric oxide (NO) in a form that can be inhaled. NO is a potent vasodilator, a compound that causes blood vessels to widen, decreasing blood pressure and allowing more blood to flow — and, therefore, more oxygen and nutrients. This is the rationale behind its therapeutic use in PH, which is defined by abnormally high blood pressure in the vessels of the lung.
The Phase 2 clinical trial iNO-PF (NCT03267108), funded by Bellerophon, is evaluating the safety and efficacy of NO delivered via INOpulse as a therapy for PF patients at risk of developing PH. The trial is being performed with multiple groups of patients, known as cohorts. The new topline data now available comes from Cohort 2.
iNO-PF’s Cohort 2 includes 44 people who were randomly selected to receive treatment with either INOpulse (45 mcg/kg) or a placebo for four months. That period is followed by an open-label extension phase, in which all participants are given the active treatment.
The results showed that, compared with those treated with placebo, patients treated with active NO exhibited statistically significant improvements in moderate-to-vigorous physical activity (MVPA). MVPA, which includes walking, climbing stairs, and yard work, increased by 14 minutes per day among those treated with INOpulse — a 20% improvement compared with the placebo group.
There also were significant improvements on the St. George Respiratory Questionnaire (SGRQ), which measures the impact of respiratory disease on daily life. Higher scores indicate a greater impact and thus reduced quality of life. On average, the total SGRQ score decreased by three points. There also were significant decreases of five points in the Activity subscore and six points on the Impact subscore.
Significant improvements in shortness of breath, as measured by the University of California, San Diego Shortness of Breath Questionnaire, also were found in participants receiving INOpulse. On average, a five-point improvement was reported.
Moreover, patients receiving INOpulse had an overall activity score improved by 100 counts per minute, representing a 7% improvement compared with the placebo group.
“The positive top-line data from Cohort 2 of iNO-PF represent a defining milestone for our INOpulse clinical development program,” Fabian Tenenbaum, Bellerophon’s CEO, said in a press release. “The significant improvement demonstrated in MVPA confirms the benefits previously observed in Cohort 1 and in our earlier trials, and positions INOpulse to potentially become the first approved therapy to address this serious unmet medical need.”
Regarding safety, INOpulse treatment was found to be safe and well-tolerated by the participants.
“The statistically significant benefit shown by INOpulse in MVPA, as well as the consistent benefit in overall activity over a four month period, are especially encouraging,” said Steven D. Nathan, MD, medical director of the advanced lung disease and lung transplant program at Inova Fairfax Hospital and chair of Bellerophon’s steering committee. “An additional positive finding was the improvement in patient reported outcomes corroborating the improvements demonstrated in the actigraphy data, pointing to the fact that patients feel better while doing more.”
“I look forward to the continued development of INOpulse, and am excited by the potential prospects of this promising therapy in PH-ILD patients who have limited ability to perform even the most basic daily tasks,” Nathan added.
Bellerophon has plans to start a Phase 3 trial testing INOpulse in the first quarter of 2020.