Am J Respir Crit Care Med. 2026 Jan 23:aamaf128. doi: 10.1093/ajrccm/aamaf128. Online ahead of print.
ABSTRACT
INTRODUCTION/BACKGROUND: Oral imatinib, a tyrosine kinase inhibitor, demonstrated efficacy in pulmonary arterial hypertension (PAH) studies but was poorly tolerated. We report here the findings of a study with a dry powder inhaled version of imatinib (AV-101).
AIMS AND OBJECTIVES: IMPAHCT (NCT05036135) was designed to assess the efficacy, safety, tolerability, and optimal dose of AV-101 as add-on treatment for PAH, using a novel phase 2b/3 adaptive study design. Here we report the phase 2b results.
METHODS: The Phase 2b part assessed 3 BID doses of AV-101 (10mg, 35mg and 70mg) vs. placebo for 24 weeks as add-on treatment in adults with PAH. Change in Pulmonary Vascular Resistance (PVR) was the primary endpoint. Secondary endpoints included the change in other hemodynamic variables, 6 Minute Walk Distance (6MWD), WHO functional class, REVEAL Lite 2 risk score, clinical worsening, clinical improvement, NT-proBNP, quality of life, safety and tolerability.
RESULTS: 202 patients were randomized. Baseline characteristics were broadly well balanced between groups. There were no significant improvements vs. placebo in PVR (42.8 dyn·sec·cm-5 in the AV-101 10 mg group, -5.5 dyn·sec·cm-5 in the AV-101 35 mg group, -57.0 dyn·sec·cm-5 in the AV-101 70 mg group, and 19.5 dyn·sec·cm-5 in the placebo group), 6MWD or other secondary endpoints, at any dose. PK measures supported delivery of drug to the lung and into the plasma. The incidence of cough increased with dose. No safety concerns were identified.
CONCLUSIONS: Add-on dry powder inhaled imatinib (AV-101) was not effective in lowering PVR at any of the studied doses in patients with PAH. The phase 3 part of the IMPAHCT study was halted.
PMID:41738079 | DOI:10.1093/ajrccm/aamaf128