Repurposed Cancer Drug Could Treat Severe Asthma

Repurposing drugs has been an increasingly popular way for researchers to explore novel options to treat various diseases. If found effective, repurposed drugs also have an expedited approval process that can further benefit patients.

The authors of a study published by the New England Journal of Medicine discovered that the cancer drug imatinib (Gleevec) targeted mast cells, which improved airway hyperresponsiveness and reduced the number of mast cells in the airway of patients with asthma.

Mast cells are a type of white blood cell that are present in the airways of patients with severe asthma, despite treatment. It has been thought that mast cells contribute to the condition and targeting the cells could improve symptoms.

"By targeting these mast cells, we can actually make a difference for our patients with severe asthma," said senior study author Elliot Israel, MD. "This is an exciting development because patients with severe asthma often have poor disease control even when adhering to our best and most aggressive therapies."

Imatinib is a precision cancer treatment that targets the process that creates mast cells, stem cell factor, and tyrosinae kinase, which is a KIT receptor that is essential for cell creation and survival, according to the study.

The study results suggest that KIT processes and mast cells contribute to severe asthma. The authors believe that imatinib and mast cell inhibitors could be effective for patients who do not respond to current therapies.

"This study shows how the investigator community begins to apply knowledge of basic disease pathogenesis to tailor interventions to specific patient populations, which leads to more effective therapy,” said James Kiley, PhD, director, Division of Lung Diseases, at the National Heart, Lung, and Blood Institute. “This is particularly the case for this patient group with a disease that is difficult to treat and that has a high morbidity rate.”

Included in the clinical trial were 62 patients with inadequately controlled severe asthma. Patients were randomized to receive imatinib or placebo and underwent a bronchoscopy with airway biopsy at baseline and at the conclusion of the study. The investigators also measured airway responsiveness and airway function.

The authors discovered that after 3 months, patients treated with imatinib had a 50% reduction in airway hyperresponsiveness compared with placebo patients, according to the study. At 6 months, the difference between cohorts was similar.

Patients treated with imatinib were also observed to have a reduction in serum tryptase — a marker for mast cells – compared with placebo patients.

Unexpectedly, the investigators discovered that patients treated with imatinib experienced the relaxation and opening of airways. However, these patients also experienced more muscle cramping and low phosphate levels compared with the placebo cohort.

Although the findings are preliminary, the authors found that patients with less eosinophils had a better response to treatment with imatinib, according to the study.

"There are several new drugs for severe asthma that target the more allergic, or eosinophilic, type of severe asthma. If confirmed, our finding -- that targeting mast cells is effective for patients who do not have eosinophilic-type asthma -- is particularly exciting because this group of patients, which make up about 40% of patients with severe asthma, have no current treatment options to control their disease,” the authors wrote.

Additional, larger-scale studies are necessary to confirm the findings and assess the long-term impact of therapy. The authors are already planning for these clinical trials, the study concluded.