Date: 2017-11-01
Type of
information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Science Translational Medicine
Company: Blueprint Medicines (USA - MA)
Product: avapritinib (BLU-285)
Action
mechanism:
- kinase inhibitor. BLU-285 is an orally available, potent and highly selective inhibitor of KIT and PDGFR?. Preclinical data have shown that BLU-285 is active across a broad spectrum of KIT and PDGFR? mutations, including PDGFR? D842V and KIT exon 17 mutations for which there are limited or no effective treatment options. Blueprint Medicines is initially developing BLU-285, an investigational medicine, for the treatment of patients with advanced GIST and advanced systemic mastocytosis.
- BLU-285 was discovered by Blueprint Medicines' research team leveraging its proprietary compound library, and the Company retains worldwide development and commercialization rights for BLU-285.
- In June 2017, BLU-285 received Breakthrough Therapy Designation from the FDA for the treatment of patients with unresectable or metastatic GIST harboring the PDGFR? D842V mutation. Previously, the FDA granted orphan drug designation to BLU-285 for the treatment of GIST. The FDA also granted Fast Track designation to BLU-285 for the treatment of patients with unresectable or metastatic GIST that progressed following treatment with imatinib and a second TKI and for the treatment of patients with unresectable or metastatic GIST in patients with the PDGFR? D842V mutation regardless of prior therapy. In addition, the European Medicines Agency has granted orphan drug designation to BLU-285 for the treatment of GIST.
Disease: gastrointestinal stromal tumors (GIST), systemic mastocytosis (SM)
Therapeutic
area: Cancer - Oncology - Rare diseases
Country:
Trial
details:
Latest
news:
- • On November 1, 2017, Blueprint Medicines announced the publication of translational data for its investigational medicine BLU-285 in Science Translational Medicine ("A precision therapy against cancers driven by KIT/PDGFRA mutations").
- Reported preclinical data and clinical case studies showed that BLU-285 is a potent and highly selective inhibitor of KIT and PDGFR? kinases, which are implicated in multiple diseases including gastrointestinal stromal tumors (GIST) and systemic mastocytosis (SM). Blueprint Medicines is currently evaluating BLU-285 in two ongoing Phase 1 clinical trials in patients with advanced GIST and patients with advanced SM, and plans to present updated results from both clinical trials in the fourth quarter of 2017.
- The paper highlighted the in-depth mechanistic evaluation conducted by Blueprint Medicines' scientists to characterize the activity of BLU-285 across a continuum of clinically relevant oncogenic KIT and PDGFR? mutations.
Key insights included: Currently available therapies for advanced GIST and advanced SM have limited activity against KIT and PDGFR? activation loop mutations, including KIT D816V, PDGFR? D842V, and additional resistance mutations located on exons 17 and 18. These mutations induce the KIT and PDGFR? proteins to adopt an active conformation, resulting in structural changes in the kinases that decrease the binding affinity of current therapeutic agents. BLU-285 was specifically designed to inhibit KIT and PDGFR? activation loop mutations.In vitro studies demonstrated potent activity of BLU-285 against activation loop mutations, as well as a broad spectrum of additional clinically relevant mutations, with a selectivity profile minimizing inhibition of other kinases. In vivo studies in multiple disease models showed BLU-285 induced potent anti-tumor effects. BLU-285 has demonstrated clinical proof-of concept in ongoing Phase 1 clinical trials in patients with advanced GIST and advanced SM.
Is
general: Yes
