PAH Clinical Trial of INOpulse Therapy Shows Benefit, New Phase 3 Study Planned
Bellerophon Therapeutics recently announced results from the final analysis of the second part of its Phase 2 clinical trial evaluating INOpulse for the treatment of pulmonary arterial hypertension (PAH), supporting the device’s continued evaluation in an upcoming Phase 3 trial.
INOpulse is a proprietary device consisting of a pulsative delivery system of nitric oxide (NO), an important agent for vasodilation and opening of the arteries. The company is currently developing three candidate INOpulse devices: one for the treatment PAH, another to treat pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD), and one for the treatment of pulmonary hypertension associated with idiopathic pulmonary fibrosis (PH-IPF).
In part 1 of the Phase 2 trial, patients who received INOpulse 75 mcg/kg ideal body weight per hour (iNO 75) therapy for at least 12 hours per day, combined with long-term oxygen therapy (LTOT), showed significant improvements on six-minute walk distance (6MWD, a measure of exercise capacity), with a mean improvement of 52.4 meters after 16 weeks of therapy.
In part 2, the trial’s long-term extension study, the 65 patients from that first part were randomized to receive either iNO 75 therapy or iNO 25 therapy (iNO 25 mcg/kg ideal body weight per hour) (iNO 25), for a minimum of 16 and a maximum of 32 months. All patients were also receiving at least one PAH therapy.
Analysis results showed that patients on the iNO 75 therapy for at least 12 hours a day, combined with LTOT, had a mean improvement in 6MWD of 55.2 meters compared to baseline. However, patients on this therapy for less than 12 hours a day showed a decrease of 18 meters compared to baseline. Likewise, patients on the iNO 25 therapy, including those LTOT, showed a decrease in 6MWD from baseline of 43.7 meters.
Results confirmed the initial analysis of the Phase 2 trial, where patients who used iNO 75 for at least 12 hours a day were seen to have the best benefit. No significant safety issues were reported in the extension study. There were two possibly related serious adverse events, but the patients continued on iNO therapy.
“The analysis supports the hypothesis generated from Part 1 of the Phase 2 study and is well aligned with the design of the Phase 3 program, for which we have agreement with the FDA through a SPA and with the European Medicines Agency through a Scientific Advice Working Party,” Jonathan Peacock, chairman and chief executive officer of Bellerophon Therapeutics, in a press release.
The Phase 3 trials are planned to begin this year in Europe and the U.S., using a second-generation INOpulse device, a smaller, lighter and improved version of that used in the now completed studies. The Phase 3 trials will recruit a total of 450 PAH patients and consist of two studies, one comparing iNO 75 with placebo, and the other comparing iNO 75, iNO 50, and placebo. All participants will also receive LTOT, and the primary endpoint is 6MWD improvement compared to placebo after 16 weeks.
Bellerophon Therapeutics is a clinical-stage biotherapeutics company developing therapies based on drugs and devices for cardiopulmonary conditions.