Aerami, Vectura Sign Deal to Develop Nebulized Imatinib

Aerami Therapeutics has entered an agreement with Vectura Group to develop and commercialize an inhaled form of imatinib — an approved cancer therapy — for the treatment of people with pulmonary arterial hypertension (PAH).

Under the agreement, Aerami will be solely responsible for developing this new imatinib formulation, but will have access to Vectura’s expertise in development services and a license to its FOX mesh nebulizer technology. FOX devices are able to deliver liquid drugs into the lungs by converting them into fine spray particles.

Aerami will purchase FOX devices and will pay Vectura upon meeting certain regulatory and sales milestones. Vectura will also receive royalties on net sales.

Aerami’s lead product, AER-901 (imatinib), is expected to enter a Phase 1 clinical trial with PAH patients in the second half of 2020, and the company is planning to ask regulatory agencies to grant orphan drug designation to the therapy candidate for PAH.

“Despite multiple products being available to treat the symptoms of PAH patients, it remains a fatal disease with substantial unmet needs,” Timm Crowder, PhD, chief operating officer of Aerami, said in a press release. “We look forward to working with Vectura, the PAH patient and clinician community to initiate clinical development this year.”

Imatinib, marketed as Gleevec by Novartis, is an approved treatment for certain cancers that also inhibits proteins — such as PDGF and c-KIT — whose signaling promote vascular remodeling in PAH.

After showing promise in animal studies, the treatment was investigated in the IMPRES Phase 3 trial (NCT00902174) for people with severe PAH receiving other standard therapies.

The trial, sponsored by Novartis, enrolled 202 patients who were randomly assigned to treatment with oral imatinib tablets or a placebo for 24 weeks. Its main goal was to determine improvements in exercise capacity, measured via the six-minute walk test, or the distance a patient could safely walk in six minutes.

Findings from IMPRES demonstrated that oral imatinib significantly improved exercise capacity and lowered vascular resistance compared with the placebo. These benefits were maintained in a long-term extension study (NCT01392495).

But a significant proportion of patients (44%) experienced serious adverse events and discontinued treatment (33%), limiting the utility of imatinib in PAH. These side effects included mostly nausea, tissue swelling, diarrhea, runny nose, cough, and vomiting.

Also, some patients experienced subdural hematomas — blood in the space between the brain and skull — which was rarely reported in prior PAH trials.

These substantial adverse events and drop-out rates stopped Novartis from pursuing oral imatinib’s approval for PAH. However, Aerami believes that it could significantly reduce the dose needed by delivering the treatment directly into the lungs, avoiding the significant side effects seen with the oral therapy.

“We believe that inhaled imatinib has the potential to improve PAH patients’ lives based on the significant efficacy demonstrated in a proof of concept Phase 3 trial completed with oral imatinib,” Crowder said.

The inhaled formulation will use the FOX nebulizer technology — a small, breath-activated inhalation system that delivers nebulized liquid treatments.

A version of these FOX devices, Breelib, is already used in Europe by PAH patients to deliver Ventavis (iloprost).