TY - JOUR
T1 - Phase 2b trial of inhaled imatinib for treatment of pulmonary arterial hypertension
AU - Hill, Nicholas S
AU - Gillies, Hunter
AU - Chakinala, Murali M
AU - Feldman, Jeremy P
AU - Hoeper, Marius M
AU - Jing, Zhi-Cheng
AU - McLaughlin, Vallerie V
AU - Rosenkranz, Stephan
AU - Escribano-Subias, Pilar
AU - Ghio, Stefano
AU - Gomberg-Maitland, Mardi
AU - Habib, Naomi
AU - Kopec, Grzegorz
AU - Langleben, David
AU - Lescano, Adrian
AU - Ramirez, Alicia
AU - Rischard, Franz
AU - Sitbon, Olivier
AU - Skride, Andris
AU - Dake, Ben T
AU - Khindri, Sanjeev
AU - Langley, Jonathan
AU - Niven, Ralph
AU - Zhang, Xiaosha
AU - Humbert, Marc
AU - IMPAHCT Investigators
N1 - © The Author(s) 2026. Published by Oxford University Press on behalf of the American Thoracic Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].
PY - 2026/4/1
Y1 - 2026/4/1
N2 - 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.
AB - 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.
KW - Humans
KW - Imatinib Mesylate/administration & dosage
KW - Male
KW - Female
KW - Middle Aged
KW - Administration, Inhalation
KW - Adult
KW - Aged
KW - Treatment Outcome
KW - Hypertension, Pulmonary/drug therapy
KW - Pulmonary Arterial Hypertension/drug therapy
KW - Double-Blind Method
KW - Protein Kinase Inhibitors/administration & dosage
KW - Walk Test
KW - Quality of Life
KW - Vascular Resistance/drug effects
UR - https://www-webofscience-com.db.rsu.lv/wos/alldb/full-record/MEDLINE:41738079
UR - https://pubmed.ncbi.nlm.nih.gov/41738079/
UR - https://www.scopus.com/pages/publications/105038289253
U2 - 10.1093/ajrccm/aamaf128
DO - 10.1093/ajrccm/aamaf128
M3 - Article
C2 - 41738079
SN - 1073-449X
VL - 212
SP - 802
EP - 812
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 4
M1 - aamaf128
ER -