Clinical Development of INOpulse for PH Continues to Move Forward, Bellerophon Reports

Bellerophon released an update on the latest data regarding its INOpulse therapy, and announced its plans to apply for the therapy’s approval as a treatment for patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD).

INOpulse is a device that uses inhaled nitric oxide (iNO), a potent vasodilator that relaxes blood vessels, to reduce blood pressure in the lungs. 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.

In January, Bellerophon announced positive results for patients in group 1 (41 patients) of the Phase 2b dose-escalation study (NCT03267108). The data demonstrated that an eight-week treatment with the lower dose of iNO (30 mcg/kg ideal body weight per hour), delivered through INOpulse, is safe and provides clinically meaningful improvements in the physical activity of patients.

Specifically, minutes of moderate to vigorous physical activity (MVPA, such as walking, climbing stairs, and doing yardwork, improved by 34% in those treated with INOpulse compared with those receiving a placebo.

In addition, patients on INOpulse treatment had no decline in overall activity levels, in contrast with those on placebo who were 12% less active. INOpulse treatment also resulted in better blood oxygen saturation (a 20% improvement compared with placebo), and lower levels of NT-ProBNP — a marker of heart failure and indicator of disease worsening.

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The company expects to announce further results of this Phase 2b study in the second half of this year.

Furthermore, based on the results obtained, Bellerophon was able to reach an agreement with the U.S. Food and Drug Administration (FDA) to change the ongoing Phase 2b trial to a Phase 2/3 study, and use MVPA as the primary outcome measure in the upcoming Phase 3 part.

“The FDA agreed with our proposal that MVPA will serve as the primary endpoint and that the ongoing Phase 2b study will be amended to a Phase 2/3 trial, providing a seamless transition into Cohort 3, which will serve as the pivotal Phase 3 trial for an efficient development program,” Fabian Tenenbaum, CEO of Bellerophon, said in a press release.

Currently, Bellerophon is recruiting patients for group 2 of the trial, which will assess a higher iNO dose (45 mcg/kg) over a longer treatment period (16 weeks). The optimal dose identified will then be used in the following Phase 3 trial. This last part of the study is the one necessary for Bellerophon to apply for INOpulse’s marketing approval.

“Cohort 2 is enrolling well, reflective of the significant interest from physicians in this study, and we expect to report top-line results and initiate the pivotal Phase 3 trial in the second half of 2019,” Tenenbaum said.

The company is also pursuing the development of this therapy for people with PH associated with other conditions, namely sarcoidosis and chronic obstructive pulmonary disease (PH-COPD).

“We recently initiated our Phase 2 study to assess the effect of iNO in PH-Sarcoidosis, another debilitating condition with no approved therapies,” Tenenbaum said.

The Phase 2 dose-escalation study (NCT03727451) is underway to address the safety and benefits of iNO in cardiac function, pulmonary vascular resistance, and exercise capacity, among other measures, in patients with PH associated with sarcoidosis. Top-line results from this study are also expected at the end of this year.

Regarding COPD, following positive results from a Phase 2a trial (NCT02267655) in PH-COPD patients — showing that the treatment could reduce the patients’ pulmonary arterial pressure and improve exercise capacity and ventilation-vasodilation — and an agreement with FDA, the company will move ahead to a Phase 2b study to evaluate multiple clinical outcomes, including exercise capacity and heart function.

“Bellerophon has achieved substantial progress in the beginning of 2019 with additional important milestones expected later this year,” Tenenbaum said. “Based on the data generated to date and the alignment with the FDA on the regulatory path forward, we believe INOpulse has the potential to be the first approved drug for this debilitating disease [PH-ILD].”