Aerovate Therapeutics, Inc. announced topline results from its study of AV-101, a new dry powder inhaled formulation of imatinib, in adults who have pulmonary arterial hypertension (PAH). The discouraging data came from phase 2b of the Inhaled iMatinib Pulmonary Arterial Hypertension Clinical Trial (IMPACHT) — a phase 2b/phase 3 randomized, double-blind, placebo-controlled, multinational trial of the drug.
The objective of the company’s phase 2b portion of IMPAHCT was to assess the efficacy, safety and tolerability of three different doses of AV-101 compared to placebo. Results showed that, while AV-101 was well tolerated across all dose groups, the study did not meet its primary endpoint for improvement in pulmonary vascular resistance (PVR) compared to placebo for any of the studied doses or show meaningful improvements in the secondary endpoint of change in six-minute walk distance (6MWD).
Primary Endpoint – ITT analysis of PVR (dynes*sec/cm^5)
| Dose | Least-squares mean difference as compared with placebo (95% CI) | P value |
| 10mg BID (N=50) | 42.8 (-80.57 to 166.09) | 0.4968 |
| 35mg BID (N=49) | -5.5 (-129.16 to 118.18) | 0.9306 |
| 70mg BID (N=51) | -57.0 (-181.14 to 67.20) | 0.3685 |
Secondary Endpoint – ITT analysis of 6MWD (meters)
| Dose | Least-squares mean difference as compared with placebo (95% CI) |
| 10mg BID (N=50) | -11.7 (-34.75 to 11.26) |
| 35mg BID (N=49) | -4.2 (-27.74 to 19.37) |
| 70mg BID (N=51) | +1.3 (-22.09 to 24.60) |
The company also reviewed data from several additional secondary endpoints of the phase 2b portion of IMPAHCT, which also failed to show meaningful improvements. Based upon these results, Aerovate, in agreement with the independent study advisory committee, is halting enrollment and shutting down phase 3 of IMPAHCT as well as the long-term extension study.
“The results of the phase 2b portion of IMPAHCT were unexpected and disappointing,” said Aerovate CEO Tim Noyes. “Our immediate focus is on transparently sharing these findings with investigators, patients and the PAH community. In the coming weeks, we will engage closely with the IMPAHCT study advisory committee and the PAH community to thoroughly discuss these data and their implications. We extend our heartfelt gratitude to all trial participants, investigators and site teams for their dedication to advancing therapeutic options for the treatment of pulmonary arterial hypertension.”
Aerovate said it plans to release full data from phase 2b of IMPAHCT at a later date.
AV-101 is an investigational, proprietary dry powder inhaled formulation of the antiproliferative drug imatinib. Developed specifically for pulmonary arterial hypertension (PAH), AV-101 targets cellular hyperproliferation and resistance to apoptosis, driven by improper signaling in cells of the distal pulmonary arteries. AV-101 is designed for delivery by an easy-to-use dry powder inhaler, directly into the lungs to maximize potential clinical benefit and limit systemic adverse effects.
