Insmed Reports Positive 12-Month Data for Once-Daily Inhaled TPIP in Pulmonary Arterial Hypertension, Showing Sustained Efficacy and Favorable Safety
核心洞察
Once-daily treprostinil palmitil inhalation powder (TPIP) demonstrated sustained improvement across all secondary efficacy endpoints at 12 months in the ongoing open-label extension study, including 6MWD, NT-proBNP, WHO Functional Class, and REVEAL Lite 2.0 score.
Patients who crossed over from placebo achieved similar clinical outcomes to those continuing TPIP, with both groups showing approximately 60% reduction in NT-proBNP and mean 6MWD improvements exceeding 54 meters.
Approximately 65% of all patients achieved Refined Low Risk status by REVEAL Lite 2.0, associated with less than 5% estimated mortality risk at three years.
Insmed Incorporated today announced positive 12-month data from the ongoing open-label extension (OLE) study evaluating treprostinil palmitil inhalation powder (TPIP), a once-daily inhaled prostanoid, in patients with pulmonary arterial hypertension (搜索) (PAH). The results demonstrated sustained improvement across all secondary efficacy measures and a favorable long-term safety profile, reinforcing the rationale for the recently initiated Phase 3 PALM-PAH registrational trial.
"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 (搜索)," 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."
Sustained Efficacy Across Multiple Measures
The OLE study, a non-placebo-controlled trial conducted at 45 sites globally, enrolled 91 eligible patients who had completed lead-in TPIP PAH studies. Patients were divided into two groups: those who continued TPIP (TPIP Continued, N=60) and those who crossed over from placebo (Placebo Crossed, N=31). The study included a 3-week blinded titration period followed by open-label treatment, with doses up to 1,280 µg once daily permitted at investigator discretion.
At Month 12, the mean improvement from baseline in six-minute walk distance (6MWD) was +55.7 meters for the TPIP Continued group and +54.1 meters for the Placebo Crossed group. NT-proBNP concentration, a key biomarker of cardiac stress, was reduced by approximately 60% in both groups, with geometric mean ratios to baseline of 0.40 and 0.41 in the TPIP Continued and Placebo Crossed groups, respectively.
WHO Functional Class I or II was achieved in 78.3% of the TPIP Continued group and 80.6% of the Placebo Crossed group, with more than 25% of patients across both groups attaining WHO Functional Class I—the least impaired category.
Clinically Meaningful Risk Reduction
The REVEAL Lite 2.0 risk score, a validated non-invasive tool for tracking disease trajectory, showed a mean improvement of 2.0 points from baseline for the TPIP Continued group and 1.4 points 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 (搜索) 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 and George M. and Linda H. Kaufman Academic Chair of Cardiology at Sentara Health. "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."
Safety and Tolerability Profile
The primary endpoint of the OLE study was long-term safety and tolerability. Once-daily TPIP therapy was generally well tolerated with no newly identified safety signals at doses up to 1,280 µg through Month 12. Among the 91 patients, treatment-emergent adverse events (TEAEs) occurred in 89.0% of patients, with serious TEAEs observed in 18.7% and severe TEAEs in 16.5%. TEAEs leading to study discontinuation were experienced by 7.7% of patients. Four deaths occurred during the study, none of which were considered related to TPIP treatment.
The most common TEAEs occurring in 5.0% or more of 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%).
Advancing to Phase 3
These 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. Topline results from the Phase 2b study of TPIP in patients with PAH were previously reported in June 2025.
TPIP is a dry powder formulation of treprostinil palmitil, a treprostinil prodrug consisting of treprostinil linked by an ester bond to a 16-carbon chain. Developed entirely in Insmed's laboratories, TPIP is administered via a capsule-based inhalation device and is being evaluated not only for PAH but also for pulmonary hypertension associated with interstitial lung disease (PH-ILD), progressive pulmonary fibrosis (PPF), and idiopathic pulmonary fibrosis (IPF). TPIP remains an investigational drug product that has not been approved for any indication in any jurisdiction.
PAH is a serious, progressive, rare disease affecting approximately 35,000 patients in the U.S., 40,000 patients in the EU5, and 15,000 patients in Japan. The disease is characterized by narrowing or obstruction of pulmonary blood vessels, leading to high blood pressure in the pulmonary arteries and symptoms including shortness of breath, chest pain, dizziness, fatigue, and weakness. Untreated PAH can be debilitating and often fatal.