TPIP may improve circulation, exercise capacity in PAH: Study
Based on positive results, Insmed plans Phase 3 trial launch in early 2026
A Phase 2b clinical trial of Insmed’s treprostinil palmitil inhalation powder (TPIP) suggested daily doses of the inhaled dry powder are well tolerated and may improve blood flow and exercise capacity in adults with pulmonary arterial hypertension (PAH).
“The statistically significant and clinically meaningful results shown with TPIP in pulmonary arterial hypertension mark a potential breakthrough for patients and the future of prostanoid therapy,” Gene Sullivan, MD, chief project strategy officer of Insmed, said in a company press release.
Following positive results from the Phase 2b trial (NCT05147805), the company plans to work with the U.S. Food and Drug Administration to design a Phase 3 trial for PAH. Insmed anticipates this trial beginning in early 2026.
Based on a separate Phase 2 trial (NCT05176951) of TPIP in pulmonary hypertension with associated interstitial lung disease (PH-ILD), the company plans to launch a Phase 3 trial for PH-ILD late this year.
Most participants reached maximum dose
Pulmonary hypertension (PH) is marked by high blood pressure in the pulmonary arteries, which pump blood from the heart to the lungs. Different triggers are associated with different types of PH. The causes of PAH include other diseases and heart defects, as well as genetic mutations and infections. PH-ILD occurs when inflammation or scarring in the lungs raises the pressure of nearby blood vessels.
To address this heightened pressure, vasodilator medications widen blood vessels, allowing for easier circulation. TPIP contains a precursor of treprostinil, a prostanoid that mimics the activity of a naturally occurring hormone called prostacyclin that helps blood vessels relax and widen.
A Phase 1 trial (NCT06091579) in healthy participants demonstrated TPIP remained in circulation for longer than Tyvaso, an inhaled treprostinil therapy. This may make TPIP more effective than currently available therapies, according to Insamed.
“TPIP was designed with the goal of fully harnessing the potential of treprostinil and providing meaningful benefit to patients,” Sullivan said.
In the Phase 2b study, the company evaluated TPIP’s safety and efficacy in people between the ages of 18 and 75 with PAH who were on stable therapies. The 102 participants were randomly assigned to receive inhaled TPIP or a placebo once daily.
For a three-week titration period, the researchers determined each individual’s maximum tolerated dosage, which they then received for the remainder of the 16-week trial. Three-quarters of participants titrated up to the maximum allowable dose of 640 micrograms.
TPIP patients saw 35% decrease in blood circulation measure
The study’s primary outcome measure was pulmonary vascular resistance (PVR), a metric of how difficult it is for blood to circulate through the lungs. After statistically adjusting for placebo effects, people in the treatment group saw a 35% decrease in PVR at the end of the trial compared with before the therapy.
Treated participants also saw a greater improvement in the distance they could walk in six minutes — 35.5 m, or 116.5 feet, longer than pretreatment — which is a standard assessment of exercise capacity. Another secondary outcome measure, levels of a biomarker for heart failure called NT-proBNP, was reduced by 60% over the course of the trial.
These unprecedented Phase 2b results unequivocally demonstrate TPIP’s potential to be a highly effective and well-tolerated once-daily prostanoid therapy for the treatment of PAH across disease severities and background treatment regimens.
Participants completed these evaluations about 24 hours after receiving treatment. This means TPIP’s effects lasted through the one-day interval between doses.
“Having met the primary endpoint with high statistical significance, as well as seeing positive results for all secondary efficacy endpoints, we are excited about TPIP’s potential to become the prostanoid of choice,” said Martina Flammer, MD, Insmed’s chief medical officer.
The majority of people in both groups, 88.4% of TPIP and 75.8% of placebo, experienced side effects that first occurred or worsened after therapy. Cough, headache, fatigue, and chest discomfort were among the adverse events that were more common in the treated group. Serious side effects occurred in 7.2% of participants in the TPIP group and 3% of the placebo group. Overall, Insmed determined participants tolerated the therapy well.
“These unprecedented Phase 2b results unequivocally demonstrate TPIP’s potential to be a highly effective and well-tolerated once-daily prostanoid therapy for the treatment of PAH across disease severities and background treatment regimens,” Sullivan said. “We look forward to expanding upon these results in the upcoming Phase 3 program.”
PH-ILD study results, which Insmed released in May, were more mixed, potentially because of the relatively small study size of 39 participants, according to the company. TPIP didn’t have a meaningful effect on blood oxygen level or supplemental oxygen requirements. However, exploratory analyses of six-minute walking distance and NT-proBNP showed trends toward improvement in the treatment group.
Participants in the PAH and PH-ILD studies are eligible for extension studies (NCT05649748 and NCT05649722, respectively). These will continue collecting long-term data on safety and efficacy.
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