Insmed reports positive 12-month TPIP open-label extension results in pulmonary arterial hypertension, supporting Phase 3 PALM-PAH development.
Written By: Anamika Koshti, Pharm D
Reviewed By: Pharmacally Editorial Team
Insmed announced on July 16, 2026, positive 12-month data from its ongoing open-label extension (OLE) study (NCT05649748) evaluating treprostinil palmitil inhalation powder (TPIP), a once-daily inhaled prodrug of treprostinil, in patients with pulmonary arterial hypertension (PAH). The ongoing 24-month, non-placebo-controlled study is evaluating the long-term safety, tolerability, and effectiveness of TPIP in patients who completed earlier TPIP PAH studies. Month 12 results showed sustained improvements across all secondary efficacy endpoints with no newly identified safety signals.
Trial Design and Patient Population
The OLE enrolled 91 patients across 45 global sites who completed lead-in TPIP studies, including the Phase 2b trial (NCT05147805). Patients previously treated with TPIP continued their established dose (TPIP Continued; n=60), while those who had received placebo (Placebo Crossed; n=31) underwent a three-week blinded titration beginning at 80 mcg once daily to a target dose of 640 mcg or their highest tolerated dose. Dose escalation up to 1,280 mcg was permitted at investigator discretion.
Sustained Efficacy Through 12 Months
Both treatment groups demonstrated comparable improvements across all secondary efficacy endpoints at Month 12.
Mean six-minute walk distance improved by 55.7 meters in the TPIP Continued group and 54.1 meters in the Placebo Crossed group. NT-proBNP concentrations decreased by approximately 60%, with geometric mean ratios to baseline of 0.40 and 0.41, respectively. WHO Functional Class I or II was achieved by 78.3% and 80.6% of patients, while more than one-quarter of patients in both groups reached Functional Class I.
Mean REVEAL Lite 2.0 scores improved by 2.0 points in the TPIP Continued group and 1.4 points in the Placebo Crossed group. Approximately 65% of patients achieved Refined Low Risk status, associated with an estimated less than 5% three-year mortality risk and about 7% one-year clinical worsening risk. Patients who switched from placebo achieved outcomes similar to those who continued TPIP treatment.
Safety Findings
The study’s primary endpoint of long-term safety and tolerability showed TPIP was generally well tolerated through Month 12, with no newly identified safety signals at doses up to 1,280 mcg.
Treatment-emergent adverse events occurred in 89.0% of patients, with serious events in 18.7%, severe events in 16.5%, and discontinuations due to adverse events in 7.7%. Four deaths occurred during the study, none considered treatment related.
The most common adverse events included headache (28.6%), cough (15.4%), nasopharyngitis (14.3%), diarrhea (11.0%), upper respiratory tract infection (9.9%), bronchitis (7.7%), dizziness (6.6%), epistaxis (6.6%), nausea (6.6%), anemia (5.5%), influenza (5.5%), and pneumonia (5.5%).
Clinical Interpretation
Gene Sullivan, M.D., Chief Product Strategy Officer of Insmed, said the sustained efficacy and favorable safety profile, together with previously reported Phase 2b results, reinforce TPIP’s potential to become a preferred prostanoid therapy for PAH. He also noted that patients who crossed over from placebo achieved similar clinical benefit by Month 12.
Raymond Benza, M.D., a Phase 2b Steering Committee member at Sentara Health, said previous validation studies showed that a one-point improvement in the REVEAL Lite 2.0 score is associated with a 23% reduction in mortality risk and a 21% reduction in clinical worsening risk, supporting advancement of TPIP into Phase 3 development.
Phase 3 PALM-PAH Program
The findings support the ongoing Phase 3 PALM-PAH trial (NCT07481981), a randomized, double-blind, placebo-controlled study evaluating once-daily TPIP over 24 weeks. The primary endpoint is change in six-minute walk distance, with additional assessments of safety, tolerability, and overall efficacy. Insmed plans to publish the full 12-month OLE results in the future.
What This Means for Patients
For people living with pulmonary arterial hypertension, a once-daily inhaled therapy such as TPIP could reduce treatment burden while providing sustained improvements in exercise capacity, functional status, and disease risk measures. Patients who switched from placebo achieved outcomes comparable to those continuing TPIP by Month 12. However, because these findings come from an open-label, non-placebo-controlled study, confirmation from the ongoing Phase 3 PALM-PAH trial will be needed before TPIP’s clinical benefit and long-term safety are fully established.
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About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.