Dosing Begins in Phase 1 Trial of Inhaled Imatinib

Dosing has begun in a clinical trial testing AER-901, Aerami Therapeutics‘ inhaled formulation of imatinib, which is being investigated as a potential treatment for pulmonary arterial hypertension (PAH).

“We are pleased to announce that the dosing of subjects in our Phase 1 trial is ongoing and that we expect to have results available later this year, which, combined with the completion of our long-term toxicology program, will allow us to quickly move into our planned Phase 2/3 trials targeted for early in 2022,” Steve Thornton, Aerami’s CEO, said in a press release.

An oral form of imatinib, marketed as Gleevec by Novartis, is approved as a treatment for certain types of cancers.

Imatinib works by blocking the activity of certain signaling proteins (e.g., PDGFR and c-KIT) that have been associated with cancer growth; their activity also is associated with changes to the body’s blood vessels that occur in PAH.

Due to its potential to ease the tightening and stiffness of pulmonary arteries, Novartis sponsored a Phase 3 clinical trial called IMPRES (NCT00902174), in which 202 participants were given oral imatinib as an add-on therapy or a placebo for 24 weeks (almost six months).

Findings from the trial showed that oral imatinib improved exercise capacity and measures of vascular function. However, nearly half of the participants experienced serious adverse side effects deemed related to imatinib’s high dose in the study, such as shortness of breath, tissue swelling, worsened pulmonary hypertension, and diarrhea. About a third of participants discontinued treatment due to the adverse events. Because of these safety results, Novartis elected not to pursue approval of oral imatinib for PAH.

The aim of Aerami’s inhaled formulation of the medicine is to target it more specifically to the lungs, avoiding toxicity in other parts of the body.

“By delivering AER-901, Aerami’s proprietary inhaled imatinib, directly to the site of the disease, we believe it has the potential to significantly reduce the dose necessary to achieve therapeutic benefit, thereby avoiding the adverse events seen with oral imatinib,” said Timm Crowder, president of Aerami.

AER-901 is administered once per day using the Vectura Group’s FOX mesh nebulizer, per an agreement made last year. A nebulizer administers the drug in a fine liquid spray.

“Our nebulized formulation and delivery system has the potential to improve efficacy through deeper lung penetration and better drug uptake while reducing the potential for side effects like cough, which is commonly associated with other inhaled technologies such as dry powder formulations,” Crowder said.

“We believe that AER-901 might, for the first time, provide the opportunity to modify the course of [PAH], and offer another important therapeutic option for patients with limited treatment options,” Thornton added.