AER-901 predicted to have better lung delivery than standard inhaler
Aerami Therapeutics plans Phase 2 trial to test therapy in PH patients
AER-901, a new inhaled formulation of imatinib delivered via a specialized device, was predicted to reach 2-3 times higher levels in the lung tissue over standard inhalers among people with forms of pulmonary hypertension (PH), according to new data from Aerami Therapeutics, its developer.
Having been proven to safely deliver imatinib to the lungs in healthy adults in Phase 1 testing, Aerami is planning a Phase 2 platform trial to test the therapy in patients with multiple types of PH, starting with pulmonary arterial hypertension (PAH) and PH associated with interstitial lung disease (ILD). The lung distribution findings and the design of the planned trial were presented by Aerami at a recent scientific conference.
“We believe that these new modeling data … strongly highlight the differentiated AER-901 profile across multiple forms of pulmonary hypertension,” Anne Whitaker, chairperson and CEO of Aerami, said in a company press release. “By optimizing delivery of imatinib to the lungs with AER-901, we believe that we can better target disease drivers … which may translate into an improved efficacy and safety profile at lower doses for patients with these devastating conditions.”
In PH, there is high pressure in the arteries of the lungs, called the pulmonary arteries. In PAH, that pressure arises from a narrowing or blockage of those blood vessels. PH can also come about as a complication of ILD, a group of lung diseases marked by inflammation and scar tissue buildup in the lungs.
Imatinib inhibits a family of enzymes called tyrosine kinases that are implicated in a process called vascular remodeling that’s believed to contribute to blood vessel narrowing in PAH and PH-ILD.
Novartis markets an oral formulation under the name Gleevec for certain types of cancer. In Phase 3 testing (NCT00902174), the therapy improved exercise capacity and blood flow for PAH patients, but had an unacceptable safety profile.
What is AER-901?
AER-901 contains a liquid formulation of imatinib that’s inhaled into the lungs via a device called a nebulizer that helps convert the liquid to a mist. It should offer the same benefits in the lungs as Gleevec, while avoiding the side effects associated with systemic exposure.
The AER-901 nebulizer is intended to overcome limitations that can arise with inhalers due to user errors. Specifically, the smart, breath-activated device controls the medication’s flow rate and provides real-time feedback to help patients learn how to inhale it.
The liquid formulation should also lead to better delivery and absorption in the lung tissue than dry-powder inhalation (DPI), a delivery mode for therapies where a dry powder is inhaled via a quick and deep breath.
In a poster presentation, researchers discussed findings from a computer-based prediction model designed to estimate how well imatinib would be deposited in the lungs with the AER-901 inhalation system relative to a hypothetical equivalent dose administered via DPI in healthy volunteers and patients with PAH or PH-ILD.
The analysis was conducted by Fluidda, which used its proprietary technology to make predictions based on lung CT scans from these groups and the assumed inhalation profiles of each medication.
Models predict more imatinib in lungs with AER-901
AER-901 was predicted to lead to significantly greater amounts of imatinib in the lungs, by more than twofold, relative to DPI across all three groups, with more than three times greater levels in deep areas of lung tissue.
The other poster presentation described the planned design of the uniPHied Phase 2 platform trial that intends to simultaneously test AER-901 across different types of PH. It will initially enroll 42 adults (ages 18-80) each with PAH or PH-ILD.
The PH-ILD patients will be allowed to continue stable regimens of background therapy, while the PAH patients must be on a stable dose of at least two PAH-specific treatments.
Participants in each group will be randomly assigned to AER-901 or an inhaled placebo for about six months. The starting dose will be 10 mg twice daily, which will be increased to a 20 mg twice daily dose over the first two months.
The trial’s main goal is to assess the change in pulmonary vascular resistance (PVR), a measure of the resistance to blood flow in the pulmonary arteries, in each group. Secondary goals include measures of pulmonary artery pressure and a biomarker of heart failure. After the trial, the participants will be eligible to enter a six-month open-label extension phase, where they’ll all receive AER-901.
The design of the platform trial “allows for expeditious and efficient evaluation of AER-901 in multiple pulmonary hypertension cohorts,” the researchers wrote on the poster. “Clinical experience from the uniPHied trial may inform similar approaches for other investigational products, potentially accelerating development of novel therapies to address high unmet need in pulmonary hypertension.”
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