Data Readout

Insmed's open-label TPIP extension in PAH tests durability, not a new efficacy bar

The Phase 2/3 extension study reports safety and functional data in the second half of 2026, extending an already-reported Phase 2b signal in pulmonary arterial hypertension.

By AppliedXLJuly 13, 2026Trial NCT05649748

Executive Summary

Insmed's open-label extension study in pulmonary arterial hypertension is set to report long-term safety and functional data in the second half of 2026, building on a completed Phase 2b readout.
Because the primary endpoint tracks treatment-emergent adverse events rather than a comparative efficacy measure, the readout's main job is to confirm tolerability holds up with continued inhaled dosing, not to prove a new efficacy claim.
The study filled to its target enrollment and has sat in Active, not recruiting status since last year, a normal state for a trial in its follow-up phase rather than a sign of trouble.
No other IP-receptor-targeted program in pulmonary arterial hypertension has reached completed Phase 2 testing, so this asset's extension data carries readthrough for treprostinil-based dosing regimens more broadly, including Insmed's newly initiated Phase 3 program.

The catalyst

Insmed said it expects to report data from the open-label extension of its Phase 2b TPIP study in pulmonary arterial hypertension in the second half of 2026. The catalyst is attached to NCT05649748, a Phase 2/Phase 3 extension study of treprostinil palmitil inhalation powder, an inhaled small molecule that acts as an IP receptor agonist. Insmed's chief executive, Will Lewis, cited the parent trial's TPIP readout in PAH in a January 9, 2026 update, tying it to the company's broader respiratory pipeline alongside brensocatib and amikacin liposome inhalation suspension programs. Insmed+1

Probability of Success

Endpoint Met49%

Completes61%

Clinical Significance50%

Regulatory93%

The endpoint bar

The registered primary endpoint is the number of participants who experience at least one treatment-emergent adverse event and the severity of those events, a safety measure rather than a comparative efficacy endpoint. Secondary endpoints track functional measures, including change in six-minute walk distance, NYHA/WHO functional class, NT-proBNP levels, and annualized clinical worsening event rate, all measured from the pre-extension baseline. Because the design is open-label with no control arm and the primary measure is safety, the readout is built to confirm durability of tolerability and functional status under continued dosing rather than to establish a new superiority claim. NCT05649748

Trial status and timing

The extension study enrolled 91 patients against its target of 91, unchanged after a downward revision from an earlier 100-patient projection recorded in April 2025. The trial moved from Recruiting to Active, not recruiting the same day enrollment was finalized, and its primary completion date has held at December 31, 2026 without a subsequent change. Insmed's own guidance on the readout window has narrowed over time, from a second-half-2026 estimate given in January and February 2026 to a third-quarter-2026 estimate by May 2026, consistent with the trial approaching its stated primary completion date rather than slipping away from it. NCT05649748+1

Competitive and regulatory frame

No other industry-sponsored trial targeting the IP receptor in pulmonary arterial hypertension has completed Phase 2 testing; the two prior IP-receptor programs in this indication and phase were both terminated. Selexipag and ralinepag are the closest direct comparators by target and mechanism, both tested in Phase 3 PAH programs, while inhaled treprostinil itself remains the modality precedent for prostacyclin-pathway dosing in this disease. Insmed has separately initiated a Phase 3 study of TPIP in pulmonary hypertension associated with interstitial lung disease and has additional Phase 3 studies planned for PAH in 2026, making the durability data from this extension relevant to how those larger programs are dosed and monitored. NCT05649748+1

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.