On Tuesday, September 18, The Mastocytosis Society and Blueprint Medicines hosted a webinar for the SM community about avapritinib (also known as BLU-285), an investigational medicine for people with systemic mastocytosis (SM).

Dr. Andy Boral, Chief Medical Officer at Blueprint Medicines, shared an update on recently presented clinical results, as well as plans for future studies in advanced, indolent and smoldering forms of SM.

For thirty days following the event, a replay of the webcast will be made available in the “Patients” section of the Blueprint Medicines website under “Patient Community Events,” located at: http://www.blueprintmedicines.com/patients/patient-community-events. The archived webcast will be available on the site about one day after the webinar.

AVAPRITINIB

Avapritinib is specifically designed to inhibit KIT D816V mutations, which have been shown to be the primary disease driver in up to 95 percent of all patients with SM. In June 2018, Blueprint Medicines presented updated clinical data from its ongoing Phase 1 EXPLORER clinical trial of avapritinib in patients with advanced SM at the 23rd Congress of the European Hematology Association (EHA). The full data is available here and summarized below, along with Blueprint Medicines’ plans for additional clinical trials for avapritinib in SM. Please listen to the webcast recording for more information.

Phase 1 EXPLORER Study Results

As of the April 30, 2018 data cutoff date, 52 people with different forms of advanced SM, including aggressive SM, SM with associated hematological neoplasm, and mast cell leukemia, were enrolled in the EXPLORER trial. At EHA, Blueprint Medicines reported:

• Avapritinib has been generally well-tolerated, with clinical investigators reporting most side effects as Grade 1 (mild) or 2 (moderate). Ten patients have discontinued treatment: 4 due to safety events, 3 due to disease progression, 2 based on investigator decisions, and 1 patient withdrew consent.
• An 83% overall response rate in evaluable patients based on modified IWG-MRT-ECNM response criteria, which were developed by SM experts to assess clinical activity in people with advanced SM.
• All evaluable patients had improvements in one or more measures of mast cell burden, such as reductions of serum tryptase, spleen size, and mast cells in the bone marrow and other organs. The proliferation of mast cells in the body is characteristic of advanced SM and can lead to organ damage.

Planned Clinical Trial Expansion

Based on encouraging results from the ongoing EXPLORER study and favorable feedback from the U.S. Food & Drug Administration (FDA), Blueprint Medicines plans to rapidly advance development of avapritinib by initiating two new clinical trials designed to support the potential registration of avapritinib across multiple subtypes of SM.

• The PATHFINDER clinical trial is a Phase 2 study for people with advanced SM, including aggressive SM, SM with associated hematological neoplasm, and mast cell leukemia. The primary objective of the trial is to see if patients respond to treatment with avapritinib, as assessed by the modified IWG-MRT-ECNM response criteria. Blueprint Medicines plans to initiate the PATHFINDER study at multiple clinical sites in the United States, Canada and Europe in the third quarter of 2018. Additional information about the trial is available at pathfindertrial.com or https://clinicaltrials.gov/ct2/show/NCT03580655.
• The PIONEER clinical trial is a Phase 2 study for people with indolent and smoldering SM. The study will initially focus on enrolling patients with indolent SM, followed by those with indolent or smoldering forms of SM. The primary objective of the trial is to see if avapritinib improves disease symptoms and quality of life, as assessed by the ISM-SAF patient-reported outcomes survey that was developed by Blueprint Medicines based on SM community input, and is specifically designed for indolent and smoldering SM. In addition, the study aims to identify a recommended dose for these subtypes of SM.

Patients who are interested in either study can contact the Blueprint Medicines study director at studydirector@blueprintmedicines.com or 1-617-714-6707 to learn more about opportunities to participate.

Importantly, Blueprint Medicines thanks the patients, families, medical investigators and clinical site staff who have participated in the Phase 1 EXPLORER study and made the progress to-date possible.