Inhaled imatinib treatment found safe in healthy people in study

Large Phase 2 trial of AER-901 in PAH and PH-ILD expected this year

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with AER-901, an inhaled formulation of imatinib that Aerami Therapeutics is developing as a treatment for two forms of pulmonary hypertension, was generally well-tolerated in a Phase 1 study conducted with healthy volunteers.

That’s according to safety data presented by Aerami at the 2023 American Thoracic Society (ATS) International Conference, held this month in San Diego. The company also presented new preclinical data showing that AER-901 may be able to deliver a therapeutic effect at doses much lower than prior oral formulations of imatinib.

“The data we presented at ATS, along with other nonclinical data and the full results of our Phase 1 clinical trial, allow us to plan for larger clinical trials that enroll people with pulmonary hypertension,” Joshua Ziel, a spokesperson for Aerami, wrote in an email to Pulmonary Hypertension News.

Based on these data, Aerami is planning later this year to launch a Phase 2 clinical trial, dubbed uniPHied, that will test AER-901 in people with pulmonary arterial hypertension, known as PAH, or pulmonary hypertension associated with interstitial lung disease, called PH-ILD.

“We’re encouraged by the AER-901 data, and we are excited to continue its development with the goal of one day providing new treatment options that help those with PH-ILD and PAH live longer and live better,” Ziel said.

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Study expects to enroll 80-100 patients to test imatinib treatment candidate

According to Ziel, chief of staff and vice president of program development at Aerami, the upcoming trial is expected to enroll 80 to 100 participants with PAH or PH-ILD. All will be randomly assigned to receive AER-901 or a placebo. Background standard-of-care therapy will be allowed for participants with PH-ILD; all those with PAH will receive standard background treatment.

The study’s main goal will be to measure the effect of the inhaled imatinib treatment on pulmonary vascular resistance — known as PVR, it’s a measure of the resistance to blood flow in the lung’s blood vessels — after about six months. Measures of heart health, exercise capacity, and functional ability also will be explored.

Participants who complete the uniPHied study are expected to be allowed to enter into an open-label extension to be monitored for long-term outcomes.

“Ultimately, we need to see the results of Phase 2 and Phase 3 clinical trials to understand if, and how AER-901 may help people with PH-ILD or PAH,” Ziel said.

Imatinib belongs to a class of medications called tyrosine kinase inhibitors; it works by blocking the activity of certain signaling molecules that are important for driving cell growth. Overactivity of these signaling molecules is thought to play a role in driving abnormal blood vessel cell growth in PAH and PH-ILD — a process called pulmonary vascular remodeling. These signaling molecules also play a role in cancer.

“We believe that AER-901 has the potential to be one of the first reverse remodeling agents in pulmonary hypertension, meaning it may help repair and reverse the damage to pulmonary arteries caused by pulmonary vascular remodeling in PH-ILD, PAH, and potentially other forms of pulmonary hypertension,” Ziel said.

“Importantly, pulmonary vascular remodeling is thought to drive pulmonary hypertension progression and severity, but there are no approved products in PH-ILD or PAH that specifically target this process,” Ziel said.

An oral formulation of imatinib, marketed as Gleevec by Novartis, is approved to treat certain types of cancer. Novartis sponsored a Phase 3 trial (NCT00902174) that tested the oral version in people with PAH. The results indicated that the treatment had a beneficial effect on patients’ exercise capacity and vascular function, but the oral therapy also caused serious side effects, leading a substantial portion of trial participants to discontinue treatment early.

By delivering the therapy directly into the lungs, AER-901 aims to get the medication straight to where it’s needed most while minimizing side effects that arise from its activity in other parts of the body.

Another inhaled formulation of imatinib, called AV-101, is being developed by Aerovate Therapeutics as a potential treatment for PAH. The therapy candidate showed a good safety profile in a Phase 1 trial last year involving healthy volunteers. Aerovate now is recruiting PAH patients for a Phase 2b/3 trial dubbed IMPAHCT that will evaluate different doses of AV-101.

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AER-901 development program will include PH-ILD

Treatment with inhaled imatinib may allow 10 times lower doses

New preclinical data on AER-901, from rat models of PH, showed that levels of the medication in the lungs were about 10 times higher with inhaled imatinib treatment compared with the therapy’s oral formulation. This suggests that AER-901 might be effective at much lower doses than the 200 to 400 mg used for the oral therapy in clinical testing, according to Aerami.

“These results suggest that we can use 10-times lower doses of AER-901 in our Phase 2 clinical trial relative to the oral imatinib doses that were previously tested,” Ziel said.

Aerami earlier had sponsored a Phase 1 trial (NCT04903730) of AER-901, which concluded dosing in December 2022. Single and multiple ascending doses of the inhaled imatinib treatment —  ranging from 5 mg to 80 mg — were assessed in 83 healthy volunteers.

“The Phase 1 study evaluated a dose range that was five to 80 times lower than the oral imatinib doses that were previously tested,” Ziel noted.

Results from the study showed that AER-901 was generally well tolerated; most side effects of treatment were deemed mild and resolved in time. The most frequently reported side effects were those that are commonly associated with inhaled therapies, like cough and throat irritation.

“In contrast to oral imatinib, which came with frequent gastrointestinal side effects like nausea, diarrhea, or vomiting, the most common side effects with AER-901 were what someone might expect from an inhaled drug,” Ziel said.

[The] important data presented at ATS and the full results of Aerami’s completed Phase 1 of AER-901 study mark significant steps forward in the development of AER-901 with the ultimate goal of addressing the critical unmet medical need for patients with PH-ILD and PAH.

Aerami said the overall findings to date support the development of this formulation.

The “important data presented at ATS and the full results of Aerami’s completed Phase 1 of AER-901 study mark significant steps forward in the development of AER-901 with the ultimate goal of addressing the critical unmet medical need for patients with PH-ILD and PAH,” Anne Whitaker, executive chairwoman of Aerami’s board of directors, said in a company press release.

“The positive results strongly support our path forward into Phase 2,” Whitaker added.

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