RARE Daily

Aerovate’s Stock Craters After Reporting Phase 2b Trial Failure in PAH

June 18, 2024

Rare Daily Staff

Shares of Aerovate Therapeutics sank 93 percent after it reported that AV-101, a novel dry powder inhaled formulation of imatinib, did not meet the primary endpoint in a phase 2b trial in adults with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure (hypertension) in the arteries of the lungs for no apparent reason. Symptoms of PAH include shortness of breath (dyspnea) especially during exercise, chest pain, and fainting episodes.

The exact cause of PAH is unknown and although treatable, there is no known cure for the disease. PAH usually affects women between the ages of 30-60. Individuals with PAH may go years without a diagnosis, either because their symptoms are mild, nonspecific, or only present during demanding exercise. However, it is important to treat PAH because without treatment, high blood pressure in the lungs causes the right heart to work much harder, and over time, this heart muscle may weaken or fail. The progressive nature of this disease means that an individual may experience only mild symptoms at first, but will eventually require treatment and medical care to maintain a reasonable quality of life.

AV-101 is an experimental, proprietary dry powder inhaled formulation of the antiproliferative drug imatinib. Developed specifically for 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.

The objective the phase 2b portion of the Inhaled iMatinib Pulmonary Arterial Hypertension Clinical Trial (IMPAHCT), a phase 2b/phase 3, randomized, double-blind, placebo-controlled, multi-national trial was to assess the efficacy, safety and tolerability of three different doses of AV-101 compared to placebo. The primary endpoint for the Phase 2b portion of IMPAHCT is change in PVR compared with 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 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).

Aerovate 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 the phase 3 portion of IMPAHCT as well as the long-term extension study.

Aerovate plans to release full data from the phase 2b portion of IMPAHCT at a later date, the timing of which is to be determined.

“The results of the phase 2b portion of IMPAHCT were unexpected and disappointing,” said Tim Noyes, CEO of Aerovate. “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.”

Photo: Tim Noyes, CEO of Aerovate

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