Treprostinil Palmitil Inhalation Powder (TPIP) shows good safety and tolerability for once-daily PH-ILD treatment

Patients with Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD) face significant morbidity and mortality. Current inhaled treprostinil formulations, while effective, often require frequent daily dosing, which can impact patient adherence and quality of life. Treprostinil palmitil (TP) is a prodrug designed to provide prolonged pulmonary vasodilation and potentially reduce dosing frequency. This study investigates the safety and tolerability of an investigational once-daily inhalation powder (TPIP) to address the burden of frequent administration in this vulnerable patient population.

This Phase 2, randomized, placebo-controlled study (NCT05176951) enrolled 39 adults with PH-ILD, randomizing them 3:1 to receive Treprostinil Palmitil Inhalation Powder (TPIP) (n=29) or placebo (n=10) for 16 weeks. TPIP was up-titrated from 80 µg to each patient's maximum tolerated dose, up to 640 µg once daily. The primary endpoint was safety and tolerability. Secondary endpoints included pharmacokinetics of TP and treprostinil, while exploratory endpoints assessed clinical worsening, change in 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.

TPIP was well tolerated, with 79.3% of patients achieving the maximum 640 µg once-daily dose. The safety profile was consistent with known inhaled treprostinil adverse events like cough and dyspnea. Treatment-emergent adverse events (TEAEs) occurred in 93.1% of TPIP patients and 90.0% of placebo patients, with most being mild or moderate. Discontinuation due to TEAEs was lower in the TPIP group (13.8%) compared to placebo (30.0%). Serious AEs also occurred less frequently with TPIP (20.7%) versus placebo (40.0%). Following a 640 µg TPIP dose, the treprostinil elimination half-life was 7.1 h. Exploratory efficacy trends were promising:

Clinical worsening was observed in only 3 (10.3%) TPIP patients compared to 5 (50.0%) placebo patients. Improvements were also observed in 6MWD and NT-proBNP levels with TPIP treatment, suggesting potential clinical benefits beyond safety.