공고 • Jul 16
Insmed Announces Positive 12-Month Data From Ongoing Open-Label Extension Study Of Treprostinil Palmitil Inhalation Powder (TPIP) In Patients With Pulmonary Arterial Hypertension
Insmed Incorporated 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. 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: Mean improvement from baseline for 6MWD was +55.7 meters for the TPIP Continued group and +54.1 meters for the Placebo Crossed group. 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. 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. 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. 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. Treprostinil palmitil inhalation powder (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. TPIP is a potentially highly differentiated prostanoid being evaluated as a once-daily therapy for the treatment of patients with PAH, pulmonary hypertension associated with interstitial lung disease (PH-ILD), progressive pulmonary fibrosis (PPF), and idiopathic pulmonary fibrosis (IPF). TPIP is administered in a capsule-based inhalation device. TPIP is an investigational drug product that has not been approved for any indication in any jurisdiction. The 24-month open-label extension (OLE) study of treprostinil palmitil inhalation powder (TPIP) in patients with pulmonary arterial hypertension (PAH) was designed to evaluate the long-term safety, tolerability, and effectiveness of TPIP administered once daily in patients who completed the lead-in TPIP PAH studies. The OLE is being conducted at 45 sites globally and enrolled 91 eligible patients. The study included a 3-week blinded titration period followed by open-label treatment. Patients who received TPIP in the lead-in studies (TPIP Continued) received their achieved dose of TPIP; patients who received placebo in the lead-in studies (Placebo Crossed), or had delayed rollover, underwent titration starting at 80 µg once daily up to their target dose (i.e., 640 µg or highest tolerated dose) over three weeks. Further escalation up to 1,280 µg was permitted after the initial titration period at investigator discretion to optimize clinical benefit. Outcomes were evaluated against the Phase 2b lead-in study in PAH (NCT05147805) pre-randomization baseline values for relevant measurements. The primary endpoint is evaluating long-term safety and tolerability, including treatment-emergent adverse events (TEAEs) and TEAEs by severity. Secondary endpoints include change from lead-in study pre-randomization baseline in six-minute walk distance (6MWD), N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP) concentration, World Health Organization (WHO) Functional Class, REVEAL Lite 2.0 score, and additional exploratory measures over 24 months of treatment.
