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.
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.
