12-Month TPIP OLE Data in Pulmonary Arterial Hypertension

Key Takeaways

• Month-12 findings showed continued improvement in walk distance, NT-proBNP, functional class, and REVEAL Lite 2.0 scores.
• TPIP was generally well tolerated through month 12, with no newly identified safety signals and relatively infrequent discontinuations due to adverse events.
• Patients who crossed from placebo had month-12 outcomes similar to those of patients who continued TPIP, and Insmed linked the update to ongoing Phase 3 development.

In a 12-month TPIP open-label extension update, Insmed reported that once-daily treprostinil palmitil inhalation powder was associated with an approximate 60% reduction in NT-proBNP in both PAH groups. Month-12 secondary efficacy measures also remained improved across 6MWD, WHO Functional Class, and REVEAL Lite 2.0.

The 24-month OLE was open-label and non-placebo-controlled and was designed to assess long-term safety, tolerability, and effectiveness after the lead-in TPIP PAH studies. Investigators enrolled 91 eligible patients across 45 global sites. TPIP was described as a dry powder treprostinil palmitil prodrug delivered once daily through a capsule-based inhalation device. The extension included a 3-week blinded titration for patients who crossed from placebo or had delayed rollover, starting at 80 µg once daily and increasing to 640 µg or the highest tolerated dose, while patients continuing TPIP received their achieved dose. Further escalation to 1,280 µg after the initial titration period was allowed at investigator discretion, and month-12 comparisons were referenced to pre-randomization baseline values from the lead-in study.

At month 12, mean 6MWD increased by 55.7 meters in the TPIP Continued group and 54.1 meters in the Placebo Crossed group. WHO Functional Class I or II was reported in 78.3% and 80.6% of patients, respectively, and more than one quarter of patients across groups reached Class I. Mean REVEAL Lite 2.0 scores improved by 2.0 points in the continued group and 1.4 points in the crossed group. Approximately 65% of patients achieved Refined Low Risk status.

For the primary safety and tolerability endpoint, TPIP was generally well tolerated through month 12, with no newly identified safety signals at doses up to 1,280 µg once daily. Treatment-emergent adverse events occurred in 89.0% of patients, while serious events were reported in 18.7% and severe events in 16.5%. Events leading to study discontinuation were reported in 7.7% of patients. Four deaths occurred during follow-up, and none were considered related to TPIP treatment.