Direct delivery of imatinib to the lungs in nonclinical species demonstrated increased lung exposure compared with oral or IV dosing
Formulation impacted lung exposure with dry powder demonstrating greater lung exposure than suspension or solution and greater lung exposure vs oral or IV delivery
The potential for a novel dry powder formulation of inhaled imatinib (AV-101), to lower the human dose necessary for an improved therapeutic profile in the treatment of pulmonary arterial hypertension is being explored in the currently recruiting IMPAHCT Phase 2b / Phase 3 trial
“The results from these nonclinical studies further support our development of AV-101, a dry powder formulation of imatinib administered by inhalation for the treatment of PAH,” said
The studies investigated the pharmacokinetics of imatinib in nonclinical models, including mice, rats, and cynomolgus monkeys, following delivery of imatinib formulations directly into the lungs compared to other routes of administration. Data showed that lung exposure in mice and rats following dry powder inhaled delivery was substantially higher versus oral delivery, and the dry powder formulation of imatinib enhanced lung exposure in rats over direct delivery of suspension or solution, and improved lung exposure versus oral or intravenous delivery. Repeat dosing of dry powder aerosol to rats and monkeys also suggested concentrations were maintained in the lungs after 24 hours. Measurements of the active imatinib metabolite, N-desmethyl imatinib, showed no apparent contribution to imatinib metabolism arising from the lungs. Plasma time course profiles of imatinib after direct dry powder or suspension dosing in rats were indicative of dissolution-controlled absorption. These nonclinical results suggest that the AV-101 formulation and inhaled delivery of imatinib can enhance lung exposure at a lower dose versus oral administration.
A previous Phase 1 study of AV-101 in healthy volunteers demonstrated significantly lower systemic exposure compared to oral imatinib. AV-101 was generally well-tolerated, suggesting that lower systemic exposure can potentially decrease the side-effects associated with oral imatinib for the treatment of PAH.
Aerovate continues to enroll IMPAHCT, a multi-national, placebo-controlled Phase 2b/Phase 3 trial that is evaluating the safety and efficacy of AV-101 in adults with PAH. Aerovate expects to report topline data from the Phase 2b portion of the trial in the second quarter of 2024.
A copy of the conference poster presentation will be available in the “Presentations & Events” section of Aerovate’s website at ir.aerovatetx.com.
Session: B59 –
Poster: The Influence of Route of Delivery and Formulation on the Pulmonary Pharmacokinetics of Imatinib in Nonclinical Species
Poster number: P220
Presenting author:
Date:
Time:
About AV-101
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. By targeting the proliferation and accumulation of cells in the arteries of the lungs, we believe AV-101 has the potential to provide meaningful improvements for patients beyond the capabilities of currently approved therapies. 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 published in
About PAH
PAH is a rare, progressive orphan disease with unmet medical need that affects approximately 70,000 people in
About the IMPAHCT Trial
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 portion 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. More information about this trial is available at https://clinicaltrials.gov/ct2/show/NCT05036135.
About
Aerovate is a clinical-stage biopharmaceutical company focused on developing drugs that meaningfully improve the lives of patients with rare cardiopulmonary disease. Aerovate’s initial focus is on advancing AV-101, its proprietary dry powder inhaled formulation of the drug imatinib for the treatment of patients with PAH. Learn more at aerovatetx.com or follow the company on Twitter and LinkedIn.
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Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the therapeutic potential, tolerability and clinical benefits of AV-101; the timing associated with the identification and activation of clinical sites, patient enrollment, initiation, delivery of drug supply and continuation of our Phase 2b/Phase 3 trial of AV-101 in PAH patients; the impact of the COVID-19 pandemic on our business, clinical trials, operations and goals; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in
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