Daily Inhaled TPIP Improved PAH Measures at 12 Months in OLE

Treprostinil palmitil inhalation powder (TPIP; Insmed), an investigational once-daily dry powder prostanoid prodrug, demonstrated sustained improvements across all secondary efficacy endpoints at 12 months in an ongoing open-label extension (OLE) study in patients with pulmonary arterial hypertension (PAH), Insmed announced July 16, 2026.¹ Patients who had received placebo in the lead-in Phase 2b trial and crossed over to TPIP in the OLE achieved outcomes comparable to those who had received TPIP continuously, suggesting a treatment response after delayed initiation.

The findings support advancement of the Phase 3 PALM-PAH trial, a randomized, double-blind, placebo-controlled study now enrolling patients with PAH, with change in 6-minute walk distance (6MWD) as its primary endpoint.¹

OLE Results Support PALM-PAH Phase 3 Trial

The 24-month OLE enrolled 91 patients who completed the lead-in TPIP PAH Phase 2b study (NCT05147805) across 45 global sites. Following a 3-week blinded titration period, patients in the TPIP Continued group (n = 60) resumed their achieved Phase 2b dose, while patients in the Placebo Crossed group (n = 31) titrated from 80 µg once daily to a target of 640 µg or highest tolerated dose. Dose escalation to 1,280 µg once daily was permitted at investigator discretion. Efficacy outcomes were assessed against pre-randomization baseline values from the Phase 2b lead-in study.¹

The primary endpoint was long-term safety and tolerability. Secondary endpoints — including 6MWD, N-terminal pro-B-type natriuretic peptide (NT-proBNP), World Health Organization (WHO) Functional Class, and REVEAL Lite 2.0 risk score — were exploratory in nature.¹

At month 12, mean improvement from Phase 2b baseline in 6MWD was +55.7 meters in the TPIP Continued group and +54.1 meters in the Placebo Crossed group. NT-proBNP concentration was reduced by approximately 60% in both groups, with geometric mean ratios to baseline of 0.40 and 0.41, 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; more than 25% of patients across both groups achieved WHO Functional Class I.¹

Mean REVEAL Lite 2.0 score improved by 2.0 points from baseline in the TPIP Continued group and 1.4 points in the Placebo Crossed group. Approximately 65% of patients across both groups achieved Refined Low Risk status, associated in prior REVEAL Lite 2.0 validation studies with an estimated 3-year mortality risk below 5% and approximately 7% risk of clinical worsening at 1 year.¹

"The REVEAL Lite 2.0 risk score provides a powerful, non-invasive way to track disease trajectory," said Raymond Benza, MD, George M. and Linda H. Kaufman Academic Chair of Cardiology at Sentara Health, and Phase 2b steering committee member. "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."¹

Promising Results Tempered by High AE Rates and OLE Limitations

Treatment-emergent adverse events (TEAEs) occurred in 89.0% of patients through month 12. Serious TEAEs were reported in 18.7% and severe TEAEs in 16.5% of patients; 7.7% discontinued due to TEAEs. There were 4 deaths, none considered related to TPIP. The most common TEAEs occurring in ≥5% 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%). No new safety signals were identified at doses up to 1,280 µg.¹

Nicholas Kolaitis, MD, MS, associate professor of medicine at the University of California – San Francisco, previously addressed high AE rates with TPIP in data from a different study, noting that “[while] it seems like even though patients do have cough, [it] was not worse after starting this new formulation, which has allowed us to get to higher doses faster, and to higher doses in general… And I think that the big implication here is that it's easier to tolerate, it's easy to use. You can get to higher doses faster, so you can impact change a lot quicker in your patients, which potentially could lead to better outcomes down the line.”

Clinicians should note that this OLE is a single-arm, open-label study without a concurrent placebo control group; secondary and exploratory efficacy endpoints are not adjusted for multiplicity, and improvements reflect comparison to Phase 2b pre-randomization baseline values — meaning the TPIP Continued group's 12-month gains encompass the full treatment period beginning in the Phase 2b study, not a fresh OLE starting point. The sample sizes are small, and Insmed acknowledges that OLE data may not accurately predict results in the Phase 3 PALM-PAH randomized trial.¹ Full publication of the 12-month OLE data is planned.

These results build on Phase 2b data reported in June 2025, in which TPIP produced a 35% placebo-adjusted reduction in pulmonary vascular resistance at week 16 (least squares mean ratio, 0.65; P <.001) and a 35.5-meter improvement in 6MWD versus placebo.²

References

1. Insmed Incorporated. Insmed announces positive 12-month data from the ongoing open-label extension study of treprostinil palmitil inhalation powder (TPIP) in patients with pulmonary arterial hypertension. Press release. July 16, 2026. https://investor.insmed.com/2026-07-16-Insmed-Announces-Positive-12-Month-Data-from-the-Ongoing-Open-Label-Extension-Study-of-Treprostinil-Palmitil-Inhalation-Powder-TPIP-in-Patients-with-Pulmonary-Arterial-Hypertension

2. Insmed Incorporated. Insmed announces positive topline results from Phase 2b study of treprostinil palmitil inhalation powder (TPIP) as once-daily therapy in patients with pulmonary arterial hypertension. Press release. June 10, 2025. https://investor.insmed.com/2025-06-10-Insmed-Announces-Positive-Topline-Results-from-Phase-2b-Study-of-Treprostinil-Palmitil-Inhalation-Powder-TPIP-as-Once-Daily-Therapy-in-Patients-with-Pulmonary-Arterial-Hypertension