Date: 2015-04-24
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 50th International Liver Congress (ILC) 2015 in Vienna, Austria
Company: Blueprint Medicines (USA - MA)
Product: BLU-554
Action
mechanism:
- FGFR4 inhibitor. BLU-554 is a selective inhibitor of fibroblast growth factor receptor 4 (FGFR4).
Disease: hepatocellular carcinoma
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On April 24, 2015, Blueprint Medicines announced new preclinical data demonstrating that BLU-554, a selective inhibitor of fibroblast growth factor receptor 4 (FGFR4), has significant anti-tumor activity in models of hepatocellular carcinoma (HCC) that are dependent on FGFR4 signaling. BLU-554 induced complete tumor regression in a subset of mice harboring genomic amplification of an FGFR4-activating ligand at the highest dose levels. These data will be presented at the 50th International Liver Congress (ILC) 2015 in Vienna. BLU-554 showed significant anti-tumor efficacy and was well-tolerated in two in vivo models of HCC driven by aberrant FGFR4 signaling, one with genomic amplification of FGFR4-activating ligand FGF19 and another with FGF19 overexpression in the absence of amplification. In the preclinical data being presented at ILC, BLU-554 demonstrated:
- • Complete tumor regression in 100 percent of mice with genomic amplification of FGF19 treated for 21 days at the 100 mg/kg twice daily and 200 mg/kg once daily doses.
• Dose-dependent tumor growth inhibition in mice with overexpression of FGF19 in the absence of amplification.
- • Potent inhibition of FGFR4 and greater than 100-fold more selectivity for FGFR4 than FGFR1-3 in in vitro studies. In contrast, pan-FGFR inhibitors fail to exhibit selective inhibition of FGFR4 compared with the other family members.
- • Little to no inhibition of all other kinases.
- Abnormal activation of FGFR4 signaling is a key driver in up to 30 percent of HCC patients. The overexpression of the FGF19 ligand triggers aberrant FGFR4 signaling, leading to cell proliferation and tumor growth. FGF19 overexpression can be caused by genomic amplification of the FGF19 gene but also occurs in the absence of genomic amplification via other molecular mechanisms.
Is
general: Yes
