AV-101 trial participants have significant disease at study’s start

Aerovate says population highlights need for new therapy

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Pulmonary arterial hypertension (PAH) patients enrolled in a Phase 2b clinical trial testing AV-101, an inhaled formulation of imatinib, entered the trial with significant disease despite use of triple background therapy, according to data shared by developer Aerovate Therapeutics.

The company said the study population will allow for the clear demonstration of AV-101’s clinical benefits in this ongoing part of the IMPAHCT Phase 2/3 trial (NCT05036135), top-line results from which are expected next month.

Enrollment in the study’s Phase 3 portion also is ongoing at more than 120 sites globally. The study is seeking adults with PAH, ages 18-75, who are on stable PAH background therapy.

“We believe that we are at the beginning stages of a new era of therapeutics in PAH that have the potential to address the root cause of disease,” Tim Noyes, Aerovate CEO, said in a company press release. “We are looking forward to providing our Phase 2b data in June and advancing AV-101 development to provide a novel … treatment for patients with PAH who need more options.”

Imatinib is a compound believed to prevent the abnormal cell growth that contributes to the narrowing of the arteries in the lungs (pulmonary arteries) and subsequent high blood pressure in those arteries that characterizes PAH.

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Dry powder designed to have fewer side effects than oral formulation

An oral version of the therapy from Novartis — sold as Gleevec for certain types of cancer — showed an ability to improve blood flow and exercise capacity for PAH patients in a Phase 3 study, but had unacceptable side effects.

AV-101 is a dry powder formulation of imatinib, designed to be inhaled into the lungs through a standard inhaler. Inhaled AV-101 is expected to have similar benefits as the oral formula, but with fewer side effects.

The treatment was found in a Phase 1 trial to directly deliver imatinib to the lungs with lower systemic exposure than an oral formulation. No serious adverse events were reported.

In the Phase 2b study, 202 adults with PAH were enrolled and randomly assigned to one of three doses of AV-101, or a placebo, taken twice daily for about six months. The main goal is to test the treatment’s effects on pulmonary vascular resistance, a measure of the resistance to blood flow.

Aerovate said that the characteristics of the enrolled patients are similar to those seen in other recent trials of investigational PAH therapies, and that the group should allow for the safety and efficacy of AV-101 to be clearly demonstrated.

The mean age of trial participants is about 47 and almost 82% are women. They’ve been living with PAH for a median of about six years.

About half of the patients are in World Health Organization (WHO) functional class II, and approximately half are in class III. In both classes, normal daily activities may be somewhat or substantially limited due to shortness of breath.

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Participants’ impairments point to ‘unmet need’ for new therapy

Overall, 57% of participants are on triple background therapy with the three main classes of PAH medications: prostacyclins, endothelin receptor antagonists, and nitric oxide pathway-targeted medications.

Nevertheless, trial participants generally showed continued impairments in blood flow, function, and exercise capacity, according to Aerovate.

Aerovate presented baseline data from the Phase 2b portion of the trial at the American Thoracic Society’s 2024 international conference held May 17-22 in San Diego.

“These baseline characteristics reflect a patient population with significant disease despite treatment with two to three targeted PAH therapeutics,” said Hunter Gillies, Aerovate chief medical officer. “This underscores the unmet need for novel therapeutics with unique mechanisms of action that address the key drivers of PAH.”

Findings from the Phase 2b trial will inform the optimal dose to be used in Phase 3. Participants in the Phase 3 portion are being randomly assigned to receive AV-101 or a placebo for about six months, with the main goal of evaluating the treatment’s effects on exercise capacity.

While multiple doses of AV-101 are initially being tested, the optimal dose selected in Phase 2b will be used once it is identified.

“We believe we are well positioned to move AV-101 forward efficiently through Phase 3 development without compromising the scientific rigor required to optimize the dose of a new investigational drug for patients,” Gillies said.

Another version of imatinib, AER-901, is being developed by Aerami Therapeutics for people with forms of pulmonary hypertension. Like AV-101, AER-901 is inhaled directly into the lungs, but it comes as a liquid formulation rather than a dry powder.

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