What were the main efficacy results of the TPIP Phase 2b PAH study?

The study met its primary endpoint, showing a 35% placebo-adjusted reduction from baseline in pulmonary vascular resistance (LS mean ratio 0.65; p<0.001). Secondary endpoints also met: a 35.5-meter placebo-adjusted improvement in six-minute walk distance (p=0.003) and a 60% placebo-adjusted reduction in NT-proBNP (p<0.001).

How well was TPIP tolerated?

Treatment-emergent adverse events occurred in 88.4% of TPIP patients versus 75.8% on placebo. Serious adverse events were 7.2% vs. 3.0%, and severe adverse events were 5.8% vs. 3.0%. Discontinuation due to adverse events was 5.8% on TPIP and none on placebo. The most common adverse events were cough (40.6% vs. 21.2%) and headache (31.9% vs. 15.2%).

What are Insmed's next development steps for TPIP?

Insmed will engage with the FDA on the Phase 3 trial design for PAH. It plans to initiate a Phase 3 trial in patients with PH-ILD before the end of 2025 and a Phase 3 trial in patients with PAH in early 2026. Detailed Phase 2b results and the open-label extension results will be presented at future medical meetings.

What is the significance of efficacy being measured about 24 hours after dosing?

The company states that efficacy was evaluated approximately 24 hours after therapy was administered, which it characterizes as demonstrating sustained benefit over the 24-hour dosing period, supporting TPIP's potential as a once-daily therapy.

How many patients completed the study and entered the open-label extension?

Of the 102 randomized patients, 90% of those on TPIP (n=62) and all patients on placebo completed the study. Of the 95 patients who completed the Phase 2b study, 95% enrolled in the long-term open-label extension, which will evaluate TPIP up to a maximum dose of 1,280 µg once daily.

INSM 8-K: Regulation FD

Q: How well was TPIP tolerated?

Treatment-emergent adverse events occurred in 88.4% of TPIP patients versus 75.8% on placebo. Serious adverse events were 7.2% vs. 3.0%, and severe adverse events were 5.8% vs. 3.0%. Discontinuation due to adverse events was 5.8% on TPIP and none on placebo. The most common adverse events were cough (40.6% vs. 21.2%) and headache (31.9% vs. 15.2%).

Q: What are Insmed's next development steps for TPIP?

Insmed will engage with the FDA on the Phase 3 trial design for PAH. It plans to initiate a Phase 3 trial in patients with PH-ILD before the end of 2025 and a Phase 3 trial in patients with PAH in early 2026. Detailed Phase 2b results and the open-label extension results will be presented at future medical meetings.

Q: What is the significance of efficacy being measured about 24 hours after dosing?

The company states that efficacy was evaluated approximately 24 hours after therapy was administered, which it characterizes as demonstrating sustained benefit over the 24-hour dosing period, supporting TPIP's potential as a once-daily therapy.

Q: How many patients completed the study and entered the open-label extension?

Of the 102 randomized patients, 90% of those on TPIP (n=62) and all patients on placebo completed the study. Of the 95 patients who completed the Phase 2b study, 95% enrolled in the long-term open-label extension, which will evaluate TPIP up to a maximum dose of 1,280 µg once daily.

01—Abstract

Summary

Summary of the 8-K filed June 10, 2025. Cited figures are marked; the original filing is the authoritative source.

Insmed Incorporated (INSM) announced positive topline results from its randomized, double-blind, placebo-controlled Phase 2b study of treprostinil palmitil inhalation powder (TPIP), a once-daily therapy, in patients with pulmonary arterial hypertension (PAH).

The study met its primary endpoint and all secondary efficacy endpoints. The placebo-adjusted reduction from baseline in pulmonary vascular resistance was 35%^a (LS mean ratio 0.65; 95% CI: 0.54, 0.79; p<0.001), the placebo-adjusted improvement in six-minute walk distance was 35.5 meters (95% CI: 11.2, 60.7; p=0.003), and the placebo-adjusted reduction in NT-proBNP was 60% (LS mean ratio 0.40; 95% CI: 0.27, 0.59; p<0.001). Efficacy was measured approximately 24 hours after dosing.

The study enrolled 102 patients across 44 sites, randomized 2:1 to TPIP (n=69) or placebo (n=33) for 16 weeks. TPIP was generally well tolerated: treatment-emergent adverse events occurred in 88.4%^b of TPIP patients versus 75.8% on placebo, and treatment discontinuation due to adverse events was 5.8% on TPIP versus none on placebo. The most common adverse event was cough (40.6% vs. 21.2%).

There were no deaths in the study. Based on these results, Insmed will engage with the U.S. Food and Drug Administration regarding the Phase 3 trial design for PAH.

The company plans to start a Phase 3 trial in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) before the end of 2025 and a Phase 3 trial in PAH in early 2026. Detailed results will be presented at future medical meetings.

02—Key points

Key Highlights

Primary endpoint met: placebo-adjusted reduction in pulmonary vascular resistance of 35% (p<0.001), with all secondary efficacy endpoints also met.
Secondary endpoints: placebo-adjusted 6MWD improvement of 35.5 meters (p=0.003) and placebo-adjusted NT-proBNP reduction of 60% (p<0.001).
Efficacy was assessed approximately 24 hours after dosing, which the company presents as evidence of sustained once-daily benefit.
Study population: 102 patients randomized 2:1 to TPIP (n=69) or placebo (n=33) over 16 weeks at 44 sites globally.
Tolerability: 88.4% of TPIP patients reported treatment-emergent adverse events vs. 75.8% on placebo; 5.8% discontinued TPIP due to adverse events; no deaths reported.
Dosing: 75% of TPIP patients titrated to the 640 µg maximum allowed dose, and 90% completed the study.
Next steps: engagement with the FDA on Phase 3 design, with a PH-ILD Phase 3 trial planned before end of 2025 and a PAH Phase 3 trial in early 2026.

03—Questions

Frequently Asked Questions

What were the main efficacy results of the TPIP Phase 2b PAH study?
The study met its primary endpoint, showing a 35% placebo-adjusted reduction from baseline in pulmonary vascular resistance (LS mean ratio 0.65; p<0.001). Secondary endpoints also met: a 35.5-meter placebo-adjusted improvement in six-minute walk distance (p=0.003) and a 60% placebo-adjusted reduction in NT-proBNP (p<0.001).
How well was TPIP tolerated?
Treatment-emergent adverse events occurred in 88.4% of TPIP patients versus 75.8% on placebo. Serious adverse events were 7.2% vs. 3.0%, and severe adverse events were 5.8% vs. 3.0%. Discontinuation due to adverse events was 5.8% on TPIP and none on placebo. The most common adverse events were cough (40.6% vs. 21.2%) and headache (31.9% vs. 15.2%).
What are Insmed's next development steps for TPIP?
Insmed will engage with the FDA on the Phase 3 trial design for PAH. It plans to initiate a Phase 3 trial in patients with PH-ILD before the end of 2025 and a Phase 3 trial in patients with PAH in early 2026. Detailed Phase 2b results and the open-label extension results will be presented at future medical meetings.
What is the significance of efficacy being measured about 24 hours after dosing?
The company states that efficacy was evaluated approximately 24 hours after therapy was administered, which it characterizes as demonstrating sustained benefit over the 24-hour dosing period, supporting TPIP's potential as a once-daily therapy.
How many patients completed the study and entered the open-label extension?
Of the 102 randomized patients, 90% of those on TPIP (n=62) and all patients on placebo completed the study. Of the 95 patients who completed the Phase 2b study, 95% enrolled in the long-term open-label extension, which will evaluate TPIP up to a maximum dose of 1,280 µg once daily.

04—Continue

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