Mariana Castells, MD, PhD: Trial Results for Avapritinib, Indolent Systemic Mastocytosis

During a segment of her HCPLive interview, Mariana Castells, MD, PhD, discussed the PIONEER trial on avapritinib for indolent systemic mastocytosis (SM) and the results of her team’s research.

Castells is known for her work as both director of the Drug Hypersensitivity and Desensitization Center and of the Mastocytosis Center at Brigham Women’s Hospital. She is also a professor at Harvard Medical School.

Castells’s team’s data, presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2023 Annual Meeting in San Antonio, TX, was further explained in this interview.

In addition to participants having to have indolent SM diagnoses, they had to be 18 years of age. The sample size was 141 for the drug recipients and the placebo group was 71.

Castells explained that overall, avapritinib was shown to have achieved statistically significant improvements for each of the primary and secondary endpoints.

“An important piece of that is that the patients were already on medication,” she said. “So they had to have maximal treatment medication, so their best treatment was continued throughout the trial. So the patients did have symptoms, despite the fact that they were on their best medication.”

Castells explained that overall, avapritinib was shown to have achieved statistically significant improvements for each of the primary and secondary endpoints.

“There was a lot of improvement in abdominal pain and diarrhea severity, nausea,” she said. “...systemic symptoms like bone pain and fatigue were also improved on avapritinib as opposed to placebo. And neurocognitive, which is a really important piece, like brain fog, dizziness, and headaches. All of those symptoms were actually improved at 24 weeks.”

Castells added that her team looked beyond those 24 weeks at 48 week data.

She noted that the drug was found to be effective on pathological mast cell burden, symptoms, and participants' quality of life, with improvements continuing through to 48 weeks.

“In terms of the secondary endpoints, what we saw is more than 60% of the patients had more than a 50% reduction in tryptase,” she said. “So a dramatic decrease in the tryptase level. They also decrease in the KIT mutation. The KIT mutation is found in peripheral blood.”

For more information on the data from Castells’s team, view the full interview above.

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