Aerovate Therapeutics, Inc. presents the design of IMPAHCT (Inhaled iMatinib for Pulmonary Arterial Hypertension Clinical Trial; AV-101-002), a Phase 2b/Phase 3 trial investigating the safety and efficacy of AV-101 in adults with pulmonary arterial hypertension (PAH), at the American College of Chest Physicians Annual Meeting (CHEST 2022) in Nashville, TN. AV-101 is a dry powder inhaled formulation of the antiproliferative drug imatinib, designed to deliver high concentrations of imatinib throughout the airways and straight to diseased blood vessels in the lungs while limiting systemic exposure. Investigational AV-101 has been formulated for self-administration in which patients will perform two inhalations twice daily with a discreet, pocket-sized device designed for easy use.

In additioion to PVR and 6MWD, multiple additional endpoints will be evaluated including changes in WHO Functional Class, REVEAL Lite 2.0 risk score, NT-proBNP, and quality of life along with assessments of clinical worsening, clinical improvement, safety and tolerability, and pharmacokinetics. Patients may only participate in either the Phase 2b or Phase 3 part of the trial which includes a screening period (up to 30 days), treatment period (24 weeks), and a 30-day safety follow-up. Eligible patients will be able to stay on current PAH background therapies while in IMPAHCT.

Participants who successfully complete the IMPAHCT trial are eligible to continue AV-101 treatment in the long-term extension study, IMPAHCT-FUL (AV-101-003). It is estimated that the adaptive design of IMPAHCT has the potential to save at least 6 to 12 months compared to separate Phase 2 and Phase 3 trials, allowing for a more efficient and expedited development path. AV-101 is an investigational, proprietary dry powder inhaled formulation of the antiproliferative drug imatinib.

Developed specifically for pulmonary arterial hypertension (PAH), 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. Phase 1 results presented at the 2022 American Thoracic Society (ATS) annual meeting showed that AV-101 delivered by dry powder inhalation was generally well tolerated by healthy adult volunteers with no serious adverse events reported. Aerovate is enrolling patients in the IMPAHCT Phase 2b/Phase 3 clinical trial to evaluate the safety and efficacy of different doses of AV-101 in adults with PAH.

PAH is a rare, progressive disease characterized by abnormal cellular proliferation of the pulmonary vasculature that affects approximately 70,000 people in the United States and Europe. The disease process involves remodeling, constriction and occlusion of the small pulmonary arteries resulting in elevated blood pressure in the pulmonary circulation. PAH can cause strain on the heart, leading to limitation of physical activity, heart failure and reduced life expectancy.

Existing vasodilator drugs fail to treat the underlying cellular proliferation causing the disease. IMPAHCT (Inhaled iMatinib Pulmonary Arterial Hypertension Clinical Trial) is a multi-national, placebo-controlled Phase 2b/Phase 3 trial in adults with PAH that will continuously enroll patients as the study progresses from Phase 2b to Phase 3. The Phase 2b part of the trial will evaluate three doses of AV-101 over 24 weeks, compared to placebo, to identify an optimal dose based on the primary endpoint, change in pulmonary vascular resistance (PVR), and safety, tolerability, and other clinical measures. The Phase 3 portion of the trial will compare patients taking the optimal dose of AV-101, selected from the Phase 2b data, to placebo.

The primary endpoint of the Phase 3 portion of the trial will be change in six-minute walk distance (6MWD) over 24 weeks versus placebo.