INOpulse Device Improves Physical Activity in PH-ILD Patients, Phase 2b Trial Shows

Treatment with INOpulse for eight weeks is safe and provides clinically meaningful improvements in physical activity in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD), according to top-line results of an ongoing Phase 2b trial.

The results are from the first group of Bellerophon Therapeutics’ trial (NCT03267108), evaluating the safety and efficacy of INOpulse in PH-ILD patients, including those with pulmonary fibrosis, a type of ILD.

Patient enrollment is ongoing. More information on contacts and locations across the U.S. can be found here.

INOpulse is intended to reduce blood pressure in the lungs by using inhaled nitric oxide (iNO), a potent vasodilator that relaxes blood vessels. It is delivered via a tube in the nose, and uses a portable device about the size of a paperback book that automatically fine-tunes nitric oxide pulses to the patient’s breathing pattern.

Findings from the Phase 2b trial showed statistically significant improvements in several clinically meaningful parameters, as assessed by a wearable activity monitor (actigraphy). This scientifically valid approach aims to provide continuous real-world physical activity data. It is currently being used as the primary endpoint, or goal, in diverse late-stage clinical programs in PH and other cardiopulmonary disorders.

Group 1 included 41 patients who were randomized to receive iNO 30 (30 mcg/kg ideal body weight per hour) or a placebo. A one-week run-in stage was followed by an eight-week double-blinded treatment period.

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Results showed that patients receiving INOpulse had an 8% increase in moderate activity, which contrasted to a 26% decrease in participants on placebo. In addition, patients on iNO had no decline in overall activity levels, versus a 12% reduction for those on placebo.

Further clinically meaningful improvements were also found, including a smaller increase in NT-pro brain natriuretic peptide (BNP) — a biomarker of right ventricular failure produced in response to changes in pressure inside the heart — in patients on INOpulse (15%), compared to those on placebo (24%).

Treatment with INOpulse was also associated with improved oxygen saturation in the blood by 9%, in contrast to an 11% worsening with placebo.

INOpulse was well-tolerated and had no safety concerns.

“The results from Cohort 1 confirm the potential of INOpulse to effectively treat PH-ILD, a disease with a serious unmet medical need,” Fabian Tenenbaum, Bellerophon’s CEO, said in a press release. “Notably, the results were seen following only eight weeks of treatment in both patients at high and low risk of pulmonary hypertension.

“Based on these compelling top-line results, [we] intend to initiate discussions with the U.S. Food and Drug Administration to formalize a streamlined and efficient regulatory approval path for INOpulse in PH-ILD.”

The ongoing groups 2 and 3 will assess higher doses — iNO 45 and iNO 75 — with a longer treatment period of 16 weeks.

Projected to end by June 2021, the trial is supported by positive results in patients from a Phase 1 trial (NCT02267655) that focused, in part, on PH associated with pulmonary fibrosis.

“These results are especially exciting because they represent the first time such benefits have been observed in this difficult-to-treat patient population,” said Steven D. Nathan, MD, chair of Bellerophon’s steering committee and medical director of the Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital in Falls Church, Virginia. “I look forward to continuing with the clinical development of INOpulse in PH-ILD with a focus on these meaningful patient-centric endpoints.”

Additionally, the company is pursuing the development of INOpulse in PH associated with chronic obstructive pulmonary disease, sarcoidosis, and for patients with pulmonary arterial hypertension.