Date: 2015-03-16
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Cancer Discovery
Company: Blueprint Medicines (USA - MA)
Product: BLU9931
Action
mechanism: FGFR4 inhibitor. BLU9931 is a selective, covalent inhibitor of fibroblast growth factor receptor 4 (FGFR4).
Disease: hepatocellular carcinoma
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On March 16, 2015, Blueprint Medicines announced publication of the discovery and preclinical characterization of BLU9931, a selective, covalent inhibitor of fibroblast growth factor receptor 4 (FGFR4). The publication highlights the significant antitumor activity of BLU9931 in several in vivo models of hepatocellular carcinoma (HCC) with aberrantly active signaling of FGFR4. FGFR4, together with its ligand FGF19, are validated genomic drivers in up to one third of liver cancer patients. The discovery of BLU9931 led to the identification of a lead drug BLU-554 with improved pharmaceutical properties which Blueprint Medicines intends to advance into clinical trials in mid-2015. Data were published electronically in the most recent edition of Cancer Discovery, a journal of the American Association of Cancer Research (Hagel M. et al., “First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular carcinomas with an activated FGFR4 signaling pathway”).
The Cancer Discovery publication outlines the unique discovery process led by Blueprint Medicines’ scientists to craft selective, covalent drugs to FGFR4, which historically had been a challenging kinase for drug discovery due to the sequence similarities with the other FGFR
paralogs. In the publication, BLU9931 demonstrates:
• Greater than fifty-fold selectivity for FGFR4 relative to other FGFR family members and little to no inhibition of all other kinases;
• Dose-dependent tumor growth inhibition in a HCC cell-line xenograft model harboring genomic amplification of FGFR4 pathway components. Tumor-bearing mice experienced a complete remission for 30-days after cessation of 21-day treatment; and
• Dose-dependent tumor growth inhibition in a patient-derived HCC xenograft model, which is believed to be predictive of clinical response. BLU-554 demonstrated superior efficacy compared to sorafenib, the only systemic treatment currently approved for HCC patients.
The publication also features the genomics analysis conducted by Blueprint Medicines to investigate the molecular mechanisms underlying aberrant activation of FGFR4 signaling and confirmed the prevalence in up to one third of HCC patients.
Blueprint Medicines expects to initiate Phase I clinical trials with BLU-554 in mid-2015 and is currently preparing an Investigational New Drug (IND) application for the FDA.
