TPIP is a dry powder investigational formulation of treprostinil (TRE) palmitil, a TRE prodrug, enabling prolonged lung exposure and long-acting vasodilation with once-daily (QD) dosing. This phase 2 study (NCT05147805) assessed the efficacy, safety, and tolerability of TPIP vs placebo (pbo) in patients with WHO Group 1 PAH over 16wks.
Patients were randomized 2:1 to TPIP (80-640μg QD) or pbo, stratified by WHO functional class (II vs III) and number of baseline PAH medications. Primary endpoint was change in pulmonary vascular resistance (PVR) at 16wks. Secondary endpoints included safety and change in 6-min walk distance (6MWD) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.
Patient characteristics were similar across TPIP (n=69; 75.4% reached max dose 640μg) and pbo (n=33) groups (Table). At Wk16, TPIP showed a 35% pbo-adjusted (adj) reduction from baseline in the primary efficacy endpoint PVR (P<0.001); a 35.5m pbo-adj improvement in 6MWD (P=0.003) and 60% pbo-adj reduction in NT-proBNP (P<0.001) were also seen (Table). TPIP was generally well tolerated with no new safety concerns; all cough events were mild/moderate.
TPIP added to background therapy achieved the primary endpoint and showed improvement on 6MWD and other prespecified efficacy measures. Safety outcomes were consistent with those expected for the inhaled prostanoid class.
