Aerovate Therapeutics Announces 24-Week Topline Results from Phase 2b IMPAHCT Trial of AV-101 for Pulmonary Arterial Hypertension

Aerovate Therapeutics, Inc., based in Waltham, Massachusetts, recently disclosed the topline results from its Phase 2b clinical trial investigating AV-101 for treating pulmonary arterial hypertension (PAH). The clinical trial, named IMPAHCT, is a multi-national, randomized, double-blind, placebo-controlled study focusing on the efficacy, safety, and tolerability of AV-101, a novel dry powder inhaled formulation of imatinib.

The Phase 2b portion of IMPAHCT aimed to evaluate three different doses of AV-101 against a placebo. The primary goal was to assess changes in pulmonary vascular resistance (PVR) compared to the placebo. Secondary endpoints included changes in the six-minute walk distance (6MWD).

Unfortunately, the results revealed that AV-101 did not meet the primary endpoint of improving PVR compared to the placebo across any of the studied doses. Additionally, the secondary endpoint of change in 6MWD also showed no significant improvements. The detailed results are as follows:

Primary Endpoint – ITT analysis of PVR (dynes*sec/cm^5)
- 10mg BID (N=50): 42.8 (-80.57 to 166.09), P value: 0.4968
- 35mg BID (N=49): -5.5 (-129.16 to 118.18), P value: 0.9306
- 70mg BID (N=51): -57.0 (-181.14 to 67.20), P value: 0.3685

Secondary Endpoint – ITT analysis of 6MWD (meters)
- 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)

In light of these results, Aerovate, in consultation with the independent study advisory committee, has decided to halt the Phase 3 portion of the IMPAHCT trial and its long-term extension study. This decision follows the lack of meaningful improvements across additional secondary endpoints in the Phase 2b portion.

Tim Noyes, CEO of Aerovate, expressed disappointment with these unexpected findings. He emphasized the company's commitment to transparently sharing the results with investigators, patients, and the PAH community. The immediate next steps involve engaging with the IMPAHCT study advisory committee and the broader PAH community to thoroughly discuss the data and its implications.

Aerovate plans to release comprehensive data from the Phase 2b study at a future date, yet to be determined. As of mid-June 2024, the company holds approximately $100 million in cash, cash equivalents, and short-term investments.

AV-101 is an investigational dry powder inhaled formulation specifically developed for PAH. It targets cellular hyperproliferation and resistance to apoptosis in the distal pulmonary arteries. The formulation is designed for delivery directly into the lungs to maximize potential clinical benefits while minimizing systemic adverse effects.

The IMPAHCT trial was designed to evaluate the safety, tolerability, and efficacy of AV-101 over 24 weeks. It sought to identify an optimal dose based on changes in PVR and other clinical measures compared to a placebo.

Aerovate Therapeutics is a clinical-stage biopharmaceutical company focused on developing treatments for rare cardiopulmonary diseases. The initial focus is on advancing AV-101 for PAH treatment.