“The ASCENT study is the first pivotal trial to demonstrate both the safety and efficacy of a dry powder formulation of inhaled treprostinil (Yutrepia) in patients with PH-ILD, supporting its potential as a new therapeutic option in this population,” the researchers wrote in their abstract.
PH-ILD, including combined pulmonary fibrosis and emphysema, is progressive, characterized by elevated pulmonary artery pressure in patients with underlying lung disease, and has few therapeutic options. LIQ861 132.5 mcg is equivalent to at least 15 puffs of nebulized treprostinil, and LIQ861 159 mcg is equivalent to at least 18 puffs of nebulized treprostinil.
ASCENT Trial Data
The ASCENT trial, Cohort A, is a prospective, multicenter, open-label trial testing the safety, tolerability, and efficacy of LIQ861 in patients with PH-ILD.
The researchers enrolled 54 patients who met eligibility criteria, including a diagnosis of PH-ILD with mean pulmonary artery pressure at least 21 mmHg, pulmonary capillary wedge pressure no higher than 15 mmHg, and pulmonary vascular resistance at least 3 Wood units. Eligible patients received LIQ861 with dose titration based on tolerability and clinical response.
The primary objective was to evaluate LIQ861 safety and tolerability, with exploratory end points including changes from baseline in 6-minute walk distance, patient-reported Dyspnea-12 and EmPHasis-10 questionnaire scores, and a simplified cough score.
The mean participant age was 68.5 years, and 48.1% were male. ILD etiologies included idiopathic interstitial pneumonias in 48.1%, autoimmune ILDs in 35.2%, hypersensitivity pneumonitis in 1.9%, combined pulmonary fibrosis and emphysema in 9.3%, and other in 5.6%.
Baseline mean pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance were 33.4 mmHg, 8.6 mmHg, and 6.0 Wood units, respectively. Baseline mean 6-minute walk distance was 298 meters. Background treatment with a phosphodiesterase type 5 inhibitor was used in seven (13%) patients.
The median dose at Week 8 was 132.5 mcg four times daily and 159.0 mcg four times daily at Week 16. The median and mean improvements from baseline in 6-minute walk distance at Week 16 were +31.5 meters and +30.2 meters, respectively.
Overall, 37% of patients improved at least 40 meters, and 32% improved at least 50 meters. Dyspnea-12 improved from 10.5 at baseline to 9.2, and EmPHasis-10 improved slightly, from 23.7 to 22.2. The mean daytime simplified cough scores did not otherwise change from baseline through Week 16.
Treatment-emergent adverse events occurred in 70.4% of participants, the most common being cough in 26 (48.1%) patients, with 92% mild and 8% moderate, and headache in 10 (18.5%) patients, with 90% mild and 10% moderate. One patient (1.9%) had severe respiratory tract irritation, but no treatment-related serious adverse events were reported. Ten of 54 (18.5%) participants discontinued the study on or before Week 16, with no one discontinuing due to drug-related adverse events.
Reference
Kolaitis N, Saggar R, Ravichandran A, et al. Safety and Exploratory Efficacy Data of LIQ861 Dry Powder Inhaled Treprostinil in PH-ILD Patients: ASCENT to Week 16. Presented at: CHEST 2025, October 19-22, 2025; Chicago.
