TPIP's Efficacy Holds as PALM-ILD Advances, With Colin Church, MBBS, PhD

Treprostinil palmitil inhalation powder (TPIP) has now advanced into the phase 3 PALM-ILD program (NCT07179380), which will test the once-daily inhaled prostacyclin prodrug against placebo in a properly powered pulmonary hypertension associated with interstitial lung disease (PH-ILD) population.³ The phase 2 program behind it combined a 16-week placebo-controlled lead-in trial with a 24-month open-label extension (NCT05649722), designed primarily to generate a safety and biological signal rather than to establish efficacy.¹

Among 23 patients who continued TPIP from the lead-in trial, 6-minute walk distance remained 27.6 m above lead-in baseline at month 12 and 33.6 m above baseline at month 24. NT-proBNP stayed roughly 25% below lead-in baseline at both time points.²

Among the 8 patients who crossed over from placebo, 6-minute walk distance rose 29.0 m from open-label extension baseline at month 12 and 64.3 m at month 24. NT-proBNP fell 32% from extension baseline at month 12 and 44% at month 24, though these are descriptive comparisons rather than a controlled efficacy analysis. Clinical worsening occurred in 45.2% of extension patients and acute ILD exacerbations in 51.6%, underscoring the severity of the underlying population against which these functional and biomarker trends should be read.²

Only 16 of the 31 enrolled patients completed the 24-month extension, a sample too small to establish efficacy on its own. Colin Church, MD, consultant in pulmonary vascular and respiratory medicine at Queen Elizabeth University Hospital in Glasgow, led the extension analysis. Church spoke with HCPLive at the CHEST 2026 Annual Meeting in Phoenix about what the durability of these signals means as PALM-ILD moves forward.

HCPLive: Did the lead-in improvements hold up over time?

Colin Church, MD: Yes, and I think this is one of the more interesting observations. The patients who continued TPIP broadly maintained the improvements seen during the lead-in study. At month 24, 6-minute walk distance remained 33.6 m above the lead-in baseline and NT-proBNP remained around 25% lower. And there is an additional interesting observation: patients originally receiving placebo appeared to improve after switching to TPIP. In this small crossover group, 6MWD increased by 64.3 m at month 24 from the point at which they started active treatment, while NT-proBNP was 56% lower. However, it's important to note these are descriptive data, not a controlled efficacy comparison.

HCPLive: With only 16 completers, how much weight can these efficacy signals carry?

Colin Church, MD: Not enough to establish efficacy. This was an open-label extension designed primarily to assess long-term safety and tolerability, not to provide definitive efficacy evidence. However, the directional changes and the consistency across groups is encouraging. Thirty-one patients entered the extension, but only 16 completed the study, including 5 from the crossover group. We fully recognize the extension was not designed or powered to assess efficacy. What the efficacy data can do is generate confidence in the biological signal. The direction of change across 6MWD and NT-proBNP, together with maintenance of the original treatment effect, is encouraging. But the test of whether this represents a genuine therapeutic effect has to come from a sufficiently powered randomized trial.

HCPLive: Is there a case for prostanoids affecting the fibrosis itself?

Colin Church, MD: Yes, there is a biologically interesting hypothesis, but I would distinguish it from established clinical evidence. Prostacyclin signaling potentially has effects extending beyond vasodilation, including pathways relevant to vascular remodeling and fibrotic biology. In this extension study, FVC remained stable in both groups over long-term observation, which is interesting but cannot establish an antifibrotic effect without a randomized comparator. The really exciting question is therefore whether sustained pulmonary prostacyclin exposure might influence both the vascular and fibrotic components of disease. This is a hypothesis that now needs to be tested prospectively rather than inferred from this small extension.

HCPLive: What does PALM-ILD need to show to take TPIP further?

Colin Church, MD: For me it needs to do 3 things. First, confirm efficacy in a properly powered, placebo-controlled population. Second, show the benefit is clinically meaningful and durable rather than simply demonstrating a physiological or biomarker effect. And third, confirm once-daily TPIP remains tolerable and usable in the real PH-ILD population. This phase 2 program gives us a credible signal and reassuring long-term tolerability. PALM-ILD now has to convert that signal into definitive evidence of clinical benefit. TPIP has now progressed into the phase 3 PALM-ILD clinical development program, so this is precisely the question the larger program is intended to address.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Relevant disclosures include Insmed.

References

1. Church C, Molina-Molina M, Arias-Guillén M, et al. A phase 2 study of the safety and tolerability of treprostinil palmitil inhalation powder in patients with pulmonary hypertension associated with interstitial lung disease. Pulm Circ. 2026;16(2):e70322. doi:10.1002/pul2.70322

2. Church C, Molina M, Saggar R, et al. An open-label extension study of treprostinil palmitil inhalation powder (TPIP) in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). Presented at: CHEST 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.

3. ClinicalTrials.gov. Efficacy and safety study of treprostinil palmitil inhalation powder (TPIP) in participants with pulmonary hypertension associated with interstitial lung disease (PH-ILD) (PALM-ILD). NCT07179380. Accessed October 27, 2026. https://clinicaltrials.gov/study/NCT07179380