Mariana Castells, MD, PhD: New Trial Data on Avapritinib for Indolent Systemic Mastocytosis

In a new HCPLive interview, Mariana Castells, MD, PhD, discussed new results from the PIONEER trial of avapritinib for patients with indolent systemic mastocytosis (SM).

Castells serves as director of the Drug Hypersensitivity and Desensitization Center and the Mastocytosis Center at Brigham Women’s Hospital. She also works as a professor at Harvard Medical School.

The data Castells discussed was recently presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2023 Annual Meeting.

“So, one of the things that I wanted to put in the background is that when we started on mastocytosis in particular, particularly the patients who have a longstanding mastocytosis, their lifespan is the same as a normal person,” Castells said. “But they have a lot of what we call morbidity, meaning that they live their lives with complicated symptoms.”

Castells pointed out that symptoms can be anaphylactic events, wheezing, shortness of breath, hypotension, or passing out.

“Then those patients were treated with what we call mast cell control medication,” she said. “Those patients have increased levels of mast cell mediators, from histamine and tryptase leukotrienes, and prostaglandins. So we used medication that was targeting those kinds of mediators, which were the ones that provided the organs; what we call the organ systems.”

She added that up to around 5 years ago or so, the field did not address what had been the real driver of the disease.

“So a company…Blueprint, had already worked on a product: a tyrosine kinase inhibitor for advanced disease, avapritinib or BLU-285,” she explained. “And in conversations, they agreed that this potentially could be a really good option for patients with indolent systemic mastocytosis. And the registrational part of the study was initiated in June 2020.”

The first part of the study entailed about 40 patients choosing what was the effective and safe dose of the medication,” she said. “It used placebo, it was 25, 50, 100. And then after that, the registrational study started with the dose that was thought to be safe and effective, which was 25 mg.”

Castells further described some of the primary and secondary endpoints of the study.

“The primary endpoint of the study was to reduce the TSS score at week 24,” she explained. “The secondary endpoint was a reduction in the biomarkers of the disease.”

For more information on the trial data, view the interview segment with Castells above.

Castells has worked in a consultancy or as part of a paid advisory board for Cogent Biosciences within the past 12 months.