Blueprint Medicines Publishes Preclinical Proof-of-Concept Data on Promising New Therapy for Genomically Defined Hepatocellular Carcinoma

Strategic Insights -

Blueprint Medicines announced the publication of preclinical proof-of-concept data on a promising new therapy for patients with genomically defined hepatocellular carcinoma (HCC). The company's lead drug, BLU-554, demonstrated superior efficacy compared to sorafenib, the only systemic treatment currently approved for HCC patients. BLU-554 is a selective, covalent inhibitor of fibroblast growth factor receptor 4 (FGFR4), which is a validated genomic driver in up to one third of HCC patients.

The discovery of BLU-554 led to the identification of a lead drug with improved pharmaceutical properties, which Blueprint Medicines intends to advance into clinical trials in mid-2015. The data were published electronically in the most recent edition of Cancer Discovery, a journal of the American Association of Cancer Research. The Cancer Discovery publication outlines the unique discovery process led by Blueprint Medicines' scientists to craft selective, covalent drugs to FGFR4.

Key Takeaways:

  • BLU-554 demonstrated a complete remission for 30-days after cessation of 21-day treatment in a HCC cell-line xenograft model harboring genomic amplification of FGFR4 pathway components.
  • BLU-554 showed greater than fifty-fold selectivity for FGFR4 relative to other FGFR family members and little to no inhibition of all other kinases.
  • BLU-554 demonstrated superior efficacy compared to sorafenib, the only systemic treatment currently approved for HCC patients.
  • The prevalence of aberrantly active FGFR4 signaling is 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 U.S. Food and Drug Administration.
  • About 12% of HCC patients have a 5-year survival rate in the United States, while the incidence of HCC has tripled over the past two decades.

Statistics:

  • 33%: the prevalence of aberrantly active FGFR4 signaling in HCC patients.
  • 12%: the 5-year survival rate for HCC patients in the United States.
  • 300%: the increase in the incidence of HCC over the past two decades in the United States.

Sources:

  • Hagel M. et al., "First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular carcinomas with an activated FGFR4 signaling pathway", Cancer Discovery, a journal of the American Association of Cancer Research.
  • Blueprint Medicines' announcement, "Blueprint Medicines Publishes Preclinical Proof-of-Concept Data on Promising New Therapy for Patients with Genomically Defined Hepatocellular Carcinoma", PR Newswire, March 16, 2015.