Bellerophon Therapeutics has announced positive data from its Phase 3 clinical trial investigating INOpulse in patients with pulmonary arterial hypertension (PAH), as well as the enrollment of the first group of patients in its Phase 2b study testing INOpulse in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD).
INOpulse is a delivery device containing the active compound nitric oxide (NO), a potent vasodilator (widener of blood vessels) that is produced naturally in our bodies.
Using INOpulse helps relax patients’ airway muscles, leading to the reduction of blood pressure in the lungs, and of strain on the right ventricle of the heart.
Interim results from the Phase 3 INOvation-1 trial (NCT02725372), examining the safety, tolerability and effectiveness of INOpulse inhaled NO (iNO) treatment (75 mcg/kg) in 188 PAH patients, showed clinical improvements similar to those achieved with other approved PAH medicines.
Specifically, INOpulse decreased pulmonary vascular resistance (PVR, a measure of the extent to which the lung circulation “resists” blood flow), as compared to placebo after 16 weeks of treatment. While PVR improved with INOpulse, it worsened in the placebo group.
INOpulse also improved patients’ heart function, exercise capacity (measured by six-minute walk distance, 6MWD), and the levels of the right ventricular failure biomarker, NT-ProBNP. All these measurements worsened in the placebo-treated group.
“The collective results of INOvation-1 supports the vasodilatory performance of iNO, as well as its clinical benefits in improving hemodynamics, reducing right ventricular failure and preventing decline in 6MWD,” Fabian Tenenbaum, CEO of Bellerophon, said in a press release.
The encouraging results from the INOvation-1 study support the potential of INOpulse in treating PH-ILD patients, according to Tenenbaum.
“These results support the potential benefit that INOpulse can provide for PH-ILD patients, where there are no approved PH therapies and patients are not on any background PAH medications,” he said.
Meanwhile, Bellerophon enrolled the first group of 40 patients in the Phase 2b iNO-PF trial (NCT03267108) testing INOpulse in patients with and without pulmonary hypertension associated with pulmonary fibrosis (an ILD), and who are on long-term oxygen therapy.
Participants will be randomized to iNO 30 (30 mcg/kg) or placebo. Treatment will be carried out for one week, followed by an eight-week double-blinded treatment period. After that, participants will be offered to continue in the study, in an open-label access modality.
Study goals include change in 6MWD, right ventricular function, oxygen saturation, activity monitoring, and patient reported outcomes, among others.
“We are pleased with the enthusiasm for our iNO-PF Phase 2b study from investigators and the strong recruitment observed throughout the study. The completion of enrollment in cohort [group] one represents an important milestone for our INOpulse clinical development program and we look forward to the availability of these results early next year,” Tenenbaum said.
Bellerophon will add two more groups to the iNO-PF study to test higher doses of iNO and longer treatment duration. Group 2 will include approximately 20 individuals to receive either iNO 45 or placebo, while group 3 will include 20 patients to receive iNO 75 or placebo.
These groups will increase the blinded treatment period from eight weeks to 16 weeks. Enrollment in these groups is expected to start later this year. Additionally, the trial will be modified to have a dose-escalation study during the open-label period.
Top-line results for the first group enrolled in the iNO-PF trial are expected in January 2019, while results from groups 2 and 3 are anticipated later that year.