Dosing Complete in Phase 1 Trial of AER-901, Inhaled Imatinib

Study is testing safety, tolerability, pharmacokinetics in 83 healthy volunteers in Australia

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Dosing is complete in a Phase 1 clinical trial of AER-901, Aerami Therapeutics’ inhaled formulation of imatinib that’s being investigated to treat pulmonary arterial hypertension (PAH).

Aerami plans to advance the experimental therapy to a proof-of-concept Phase 2 trial in the first half of 2023. To do so, the company will first need to amend its investigational new drug application, which remains open with the U.S. Food and Drug Administration (FDA).

“Completion of dosing in our Phase 1 trial of AER-901 marks an important milestone toward our goal of realizing the potential of imatinib in PAH through targeted delivery to the deep lung,” Lisa Yañez, CEO of Aerami, said in a company press release. “We look forward to progressing AER-901 through clinical development and continuing on our path towards obtaining regulatory approval of AER-901 for the treatment of PAH.”

Imatinib works to block the activity of certain proteins associated with cancer growth. An oral formation of imatinib, marketed as Gleevec by Novartis, is approved to treat some types of cancer.

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The signaling pathways that imatinib works against also play a role in the abnormal cell growth and blood vessel changes — called vascular remodeling — that drive PAH progression. AER-901 would be a “reverse-remodeling” therapy for PAH., according to Aerami.

A Novartis-sponsored Phase 3 clinical trial called IMPRES (NCT00902174) evaluated oral imatinib’s effectiveness as an add-on therapy for PAH. A total of 202 patients were randomly assigned to receive it or a placebo for about six months.

Trial data showed oral imatinib was effective, leading to improvements in exercise capacity and measures of vascular function. Still, it wasn’t well tolerated and serious side effects and treatment discontinuations were common.

Benefit of inhaled imatinib

Inhaled formulations of imatinib allow the therapy’s delivery directly to the lungs, where it’s needed. This could mean a smaller dose would be effective, with improved safety.

In AER-901, imatinib is inhaled into the lungs using the FOX nebulizer licensed from the Vectura Group in 2020.

The FOX nebulizer is a hand-held device that delivers the medication in a fine liquid spray, using a mechanical flow regulator to control inhalation. It’s been deemed safe for marketing in the U.S. and Europe and a version is being used to deliver Ventavis (iloprost) to PAH patients in Europe.

The Phase 1 study (NCT04903730) was primarily designed to assess the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of AER-901 (5-80 mg) against a placebo in 83 healthy volunteers, ages 18-60, who were enrolled at a single site in Australia. Pharmacokinetics refers to a treatment’s movement into, through, and out of the body.

The trial, which began dosing last year, also evaluated once versus twice daily administration, as well as different formulations — one dissolved in sterile water and another in propylene glycol.

In a group of patients, a single dose of AER-901 was also compared to a single dose of oral imatinib. This part of the study had a crossover design, meaning all participants received both types of treatment in random order.

While the earlier trial parts were double-blind, meaning neither the participants nor investigators knew whether a placebo or AER-901 was being received, the final part was open label, meaning assignments were known to both groups.

Doses of AER-901 evaluated in the Phase 1 study were five to 80 times lower than the oral imatinib in the IMPRES trial, Aerami noted.

AER-901 currently holds orphan drug status in the U.S., a designation designed to help accelerate the development of treatments for rare diseases. Aerovate Therapeutics is also developing an inhaled formulation of imatinib for PAH, called AV-101, which was shown to be well tolerated in a Phase 1 trial earlier this year.

A Conversation With Rare Disease Advocates