July 16, 2025 — Insmed Inc. recently announced positive 12-Month data from the ongoing open-label extension (OLE) study evaluating treprostinil palmitil inhalation powder (TPIP), administered once daily in patients with pulmonary arterial hypertension (PAH, World Health Organization Group 1). The OLE study is a non-placebo-controlled trial and was designed to evaluate the long-term safety, tolerability, and effectiveness of TPIP over 24 months in patients who completed the lead-in TPIP PAH studies.
"These data from our ongoing OLE study with TPIP represent an important milestone in our efforts to fully harness the potential of treprostinil and provide meaningful benefit to patients with pulmonary arterial hypertension," said Gene Sullivan, M.D., Chief Product Strategy Officer of Insmed. "In this analysis, TPIP demonstrated sustained improvement across all efficacy endpoints and was well tolerated with no newly identified safety signals, and notably, patients who switched from placebo to TPIP in the OLE study achieved similar clinical benefit. These data, coupled with the statistically significant and clinically meaningful results from our Phase 2b randomized study, demonstrate TPIP's potential to become the prostanoid of choice for PAH patients, and we remain excited to be advancing our Phase 3 PALM-PAH study."
12-Month Results from the Ongoing OLE Study
Results for secondary efficacy endpoints demonstrated sustained improvement with TPIP in six-minute walk distance (6MWD), N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP) concentration, and World Health Organization (WHO) Functional Class, as well as a clinically meaningful improvement in REVEAL Lite 2.0 score at Month 12. Patients in the Placebo Crossed group (N=31) showed similar outcomes to patients in the TPIP Continued group (N=60) across all efficacy measures at Month 12.
The results at Month 12 were as follows:
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Mean improvement from baseline for 6MWD was +55.7 meters for the TPIP Continued group and +54.1 meters for the Placebo Crossed group.
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NT-proBNP concentration was reduced by approximately 60% in both groups with geometric mean ratios [GMR] to baseline of 0.40 and 0.41 in TPIP Continued and Placebo Crossed, respectively.
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WHO Functional Class I or II was achieved in 78.3% of TPIP Continued group and 80.6% of Placebo Crossed group patients, and more than 25% of patients across both groups achieved WHO Functional Class I.
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Mean REVEAL Lite 2.0 score improved 2.0-points from baseline for the TPIP Continued group and 1.4-points from baseline for the Placebo Crossed group. Approximately 65% of all patients achieved Refined Low Risk status, which is associated with a less than 5% estimated risk of mortality at three years and an approximately 7% risk of clinical worsening at one year.
"Pulmonary arterial hypertension is one of the most devastating diseases we face as clinicians, and these results from the ongoing TPIP OLE study give us genuine reason for optimism," said Dr. Raymond Benza, M.D., F.A.C.C., FAHA, FACP, Phase 2b PAH study Steering Committee Member, George M. and Linda H. Kaufman Academic Chair of Cardiology, Sentara Health. "The REVEAL Lite 2.0 risk score provides a powerful, non-invasive way to track disease trajectory. Previous REVEAL Lite 2.0 validation showed that a 1-point score improvement reduces risk of mortality by 23% and reduces the risk of clinical worsening by 21%. Here we saw that patients on TPIP averaged a greater than 1-point improvement from baseline, which is really meaningful for patients. Sustained improvements of this magnitude, alongside gains in exercise capacity and Functional Class, provide a strong clinical rationale to advance this therapy into Phase 3 development."
Results for the primary endpoint of safety & tolerability showed that once-daily TPIP therapy was generally well tolerated with no newly identified safety signals at doses up to 1,280 µg through Month 12. Of the 91 patients in the study, treatment-emergent adverse events (TEAEs) occurred in 89.0% of patients; serious TEAEs were observed in 18.7% of patients; and severe TEAEs were observed in 16.5% of patients in the study. TEAEs leading to study discontinuation were experienced by 7.7% of patients. There were four deaths, none of which were considered related to TPIP treatment. The most common TEAEs through Month 12 occurring in 5.0% or more of all patients were 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%).
The 12-Month OLE findings support the continued clinical development of TPIP and the recent initiation of PALM-PAH, a Phase 3, randomized, double-blind, placebo-controlled trial evaluating once-daily TPIP in patients with PAH over 24 weeks. The primary endpoint of PALM-PAH is change in 6MWD, with additional assessments of safety, tolerability, and overall efficacy. Insmed plans to publish the 12-Month results from this OLE study in the future. Topline results from the Phase 2b study of TPIP in patients with PAH were previously reported in June 2025.
July 16, 2026 
