Bellerophon Therapeutics announced this week that its Phase 3 clinical trial of pulsatile inhaled nitric oxide (iNO) for World Health Organization (WHO) Group 1 PH (pulmonary arterial hypertension, or PAH) was discontinued for futility August 7, after a planned interim analysis.
Nitric oxide (NO) is a molecule naturally produced in the body that helps many blood vessels relax and open, lowering the blood pressure in that area. One area of the body that makes this molecule is the cells composing the innermost layer of the blood vessels, the endothelium, which acts on the next layer of the blood vessels’ smooth muscle cells, to help the blood vessels relax and open. Studies have shown that people with PAH do not have as much NO as people without PH. In the hospital, NO is given to patients as a gas mixed with oxygen, as an inhaled nitric oxide (iNO) and is expected to lower the blood pressure in the lungs. However, iNO has not been used frequently outside of the hospital, as the effects of the molecule disappear quickly after stopping the medication. Bellerophon’s study sought to examine if iNO therapy outside of the hospital, through the INOpulse® system, could help patients with pulmonary hypertension (PH), including PAH, PH associated with interstitial lung disease (PH-ILD), and PH associated with chronic obstructive pulmonary disease (PH-COPD).
In 2016, Bellerophon launched the Phase 3 clinical trial (INOvation-1) involving more than 100 clinical sites around the world and a target of 200 PAH patients to primarily test whether those receiving iNO therapy had a greater change in six-minute walk distance (6MWD) after 18 weeks on the therapy, as compared to participants receiving a placebo. Bellerophon worked with the Food and Drug Administration (FDA) in designing the trial to build in an interim analysis when 75 patients had completed the study (about 38 percent of the total patients targeted to participate). The results of this analysis would inform the company whether they were able to 1) stop the trial because the drug clearly worked; 2) continue the study as originally planned; 3) adjust the number of patients involved if the results were different than expected; or 4) stop the study because there was no clear difference or there were safety concerns.
The external committee monitoring the study (Data Monitoring Committee (DMC)) that performed the interim analysis found that PAH patients on the therapy, in general, did not walk further on their 6MWT compared to participants receiving the placebo. The analysis also did not demonstrate significant safety concerns. With this data, Bellerophon decided this week to discontinue the study in PAH. People participating in the INOvation-1 trial will be contacted by their health care teams about when and how to discontinue the therapy.
Despite the results in the PAH study, the INOpulse® program will continue to be tested in another type of PH, WHO Group 3 PH (PH due to chronic lung disease). Bellerophon is leading a Phase 2b clinical trial of iNO in certain people with PH-ILD. The study expects to enroll approximately 40 people with PH-ILD at 16 clinical sites across the U.S. The company also has announced the design for a Phase 2b trial of iNO in PH-COPD, expecting to enroll approximately 90 PH-COPD patients. Bellerophon announced positive results for iNO in both PH-ILD and PH-COPD in early, smaller clinical trials. However, these results will need to be confirmed in larger studies involving more patients.