The Phase 2 long-term extension study indicated a sustained benefit to PAH 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). In Part 1 of the Phase 2 study, these patients showed a mean improvement in 6 minute walk distance (6MWD) of 52.4 meters after 16 weeks of therapy. In Part 2 of the study, after 16 to 32 months of treatment, the patients who remained on iNO 75 for at least 12 hours a day combined with LTOT continued to maintain a mean increase in 6MWD of 55.2 meters. None of these patients had a decrease in 6MWD. Patients, including those on LTOT, who were on either iNO 25 mcg/kg ideal body weight per hour (iNO 25) or maintained therapy for less than 12 hours per day had on average a decrease in 6MWD.
A recent study by Farber et al. shows that “worsening of the 6MWD was strongly and significantly associated with a poor prognosis.” (REVEAL Registry, Farber et al., J Heart Lung Transpl., 2015).
These data directly support the design of the planned Phase III trial.
Data from Long-term Extension Analysis
Following 16 weeks of blinded therapy in Part 1 of the trial, in Part 2 of the trial 65 patients were randomized to receive iNO 25 or iNO 75. The long-term extension analysis was performed after patients had completed between 16 and 32 months of INOpulse treatment, and data from the long-term extension analysis was compared to baseline measurements taken at the beginning of Part 1 of the trial. All patients in the trial were on at least one approved PAH therapy, and most were on two or three PAH therapies.
The long-term extension analysis showed the following:
- Patients on LTOT in the iNO 75 dose treatment arm who remained on INOpulse therapy for at least 12 hours a day had a mean improvement of 55.2 meters as compared to baseline (n=7).
- Patients on LTOT in the iNO 75 dose treatment arm who remained on INOpulse therapy for less than 12 hours a day showed a mean decrease of 18.0 meters as compared to baseline (n=6).
- Patients in the iNO 25 dose treatment arm, including those on LTOT, had a mean decrease of 43.7 meters from baseline (n=12).
For patients in the long-term extension study, no significant safety issues have been found with no reports of methemoglobin elevation and no adjudicated cases of pulmonary rebound. Only 2 Serious Adverse Events have been reported as possibly related, with these subjects continuing on iNO therapy.
These findings also confirmed a recently released interim analysis of the Phase II data which was performed at 12 months after entry into the study. The 12 month analysis also found that LTOT patients who used iNO 75 for at least 12 hours a day had the greatest benefit.
Phase 3 Development Program
The key elements of the planned U.S. and EU Phase 3 development program are:
- The Phase 3 program will consist of two clinical trials totaling 450 patients; one trial with two treatment arms (iNO 75 and placebo) and one with three treatment arms (iNO 75, iNO 50 and placebo). Each treatment arm will consist of approximately 90 patients.
- All patients in the trials will be on LTOT.
- Each trial will have a run-in period of two weeks to ensure compliance. Patients who do not stay on the therapy for at least 16 hours a day during this period will be replaced.
- The primary endpoint is improvement in 6MWD compared to placebo after 16 weeks.
- The secondary endpoint is Time to Clinical Worsening (TTCW), with analysis pooled across both trials. Patients will stay on therapy until the last patient visit measuring 6MWD. One component of the definition of TTCW is decrease in 6MWD.
The Phase 3 trials will utilize the second-generation INOpulse device, which is considerably smaller and lighter (approximately 2.5 lbs.) than the original INOpulse DS device used in the Phase 2 study (approximately 7.5 lbs.). In addition to the significant reduction in size and weight, the INOpulse device also has an improved user interface and better breath detection technology, made possible by the Company’s proprietary tri-lumen cannula.
About Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH) is a rare, chronic and currently incurable disease that causes the walls of the arteries of the lungs to tighten and stiffen. Estimates suggest that there are about 35,000 patients diagnosed with PAH in
Bellerophon Therapeutics is a clinical-stage biotherapeutics company focused on developing innovative therapies at the intersection of drugs and devices that address significant unmet medical needs in the treatment of cardiopulmonary diseases. The Company is currently developing three product candidates under its INOpulse® program, a proprietary pulsatile nitric oxide delivery device. The first is for the treatment of pulmonary arterial hypertension (PAH), for which the Company intends to commence Phase 3 clinical trials in 2016. The second is for the treatment of pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD), which is in Phase 2 development and the third candidate is for the treatment of pulmonary hypertension associated with Idiopathic Pulmonary Fibrosis (PH-IPF). The Company’s plans also call for the completion of further work on the use of INOpulse to treat PH-COPD and PH-IPF during 2016. For more information, please visit www.bellerophon.com.
Any statements in this press release about Bellerophon’s future expectations, plans and prospects, including statements about the clinical development of its product candidates, regulatory actions with respect to the Company’s clinical trials and expectations regarding the sufficiency of the Company’s cash balance to fund clinical trials, operating expenses and capital expenditures, and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary or interim results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, expectations for regulatory approvals, the FDA’s substantial discretion in the approval process, availability of funding sufficient for our foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the “Risk Factors” section of the Company’s most recent filings with the
Contact At Bellerophon:
Amy Edmonds, Vice President (908) 574-4765 At Rx Communications Group: Melody Carey(917) 322-2571