INOpulse Improves Physical Activity of ILD Patients at Risk of PH, Phase 2/3 Results Show

Bellerophon Therapeutics’ vasodilator INOpulse increased physical activity and improved quality of life in people with interstitial lung disease (PH-ILD) who are at risk of pulmonary hypertension, top-line results from a Phase 2/3 clinical trial show.

These results are from the second group of patients taking part in the double-blind, placebo-controlled iNO-PF trial (NCT03267108), which is testing the effects of different dosages of INOpulse in three groups of people diagnosed with pulmonary fibrosis and are at risk of developing PH.

This group included 44 participants, who were randomly assigned to either 45 mcg/kg INOpulse or a placebo for four months. This phase is then followed by a 16-week open-label extension phase where all participants receive INOpulse at 45 mcg/kg for eight weeks and 75 mcg/kg for another weeks.

Treatment with INOpulse improved moderate-to-vigorous physical activity (MVPA) by 14 minutes a day, corresponding with a  significant improvement of 20%. The overall activity score showed an increase of 100 counts per minute, or a 7% improvement.

In addition, the treatment also led to improvements in the St. George Respiratory Questionnaire (SGRQ), a 50-item questionnaire developed to measure the quality of life of patients with respiratory diseases. It is divided into three subscales: symptoms, activity, and impacts (26 items). For each subscale and for the overall questionnaire, scores range from zero (no impairment) to 100 (maximum impairment).

Researchers saw an overall SGRQ total score improvement of three points. SGRQ’s activity score improved by five points, and SGRQ’s Impact score by six points.

Results also showed a five-point improvement in the University of California, San Diego Shortness of Breath Questionnaire — a 24-item questionnaire that assesses self-reported shortness of breath while performing a variety of activities of daily living.

“The top-line results from Cohort 2 in the iNO-PF study are exciting and highlight the potential therapeutic benefit of INOpulse,” 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, said in a press release.

“It is validating and reassuring to see the results from Cohort 2. 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 considering that this patient population has a median life expectancy of approximately 18 months,” he added.

The INOpulse treatment was also found to be safe and well tolerated by the participants.

“The positive top-line data from Cohort 2 of iNO-PF represent a defining milestone for our INOpulse clinical development program,” said Fabian Tenenbaum, Bellerophon’s CEO. “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.”

Following these promising results, the company hopes to start a Phase 3 trial in the first quarter of 2020.

“As previously agreed upon with the U.S. Food and Drug Administration, MVPA will serve as the primary endpoint for the Phase 3 study, which we expect to initiate in the first quarter of 2020,” Tenenbaum said.

In PH-ILD, the pulmonary arteries that transport blood from the heart to the lung get narrow, causing increased blood pressure. This extra tension impairs cardiac function, mainly the heart’s right side ability to pump out blood to the lungs.

INOpulse is a treatment that uses inhaled nitric oxide, which is a powerful vasodilator that relaxes and widens blood vessels.

The first group in the iNO-PF trial included 41 participants, of whom 23 received 30 mcg/kg INOpulse for eight weeks, and the remaining took a placebo.

Results from this group of participants showed that INOpulse increased MVPA by 33% in people with an intermediate or high risk of PH, and by 28% in those with a low risk of PH, compared with the placebo group. Participants who received INOpulse could spend significantly more time performing physical tasks than those on the placebo.

“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 said.