Blueprint Medicines Announces Proof-of-Concept Data from Global Phase 1 Clinical Trial of BLU-554


Blueprint Medicines Corporation , a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases announced data from its ongoing Phase 1 trial evaluating BLU-554, an investigational medicine for the treatment of advanced hepatocellular carcinoma (HCC).

Blueprint Medicines is developing BLU-554 as a potent, highly selective inhibitor of fibroblast growth factor receptor 4 (FGFR4). The data are being presented on Tuesday, November 29, 2016, at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany.

"We desperately need new treatment options for patients with liver cancer, the second leading cause of cancer deaths worldwide," said Richard Kim, M.D., Moffitt Cancer Center, an investigator for the study. "Unlike many other tumor types, there are no biomarker-driven targeted therapies currently approved for HCC, the most common form of liver cancer.  These preliminary data are exciting as they suggest BLU-554 may offer the first targeted therapy in a biomarker-defined group of patients with advanced HCC. I am excited to evaluate BLU-554 in the expansion portion of the Phase 1 clinical trial, where we are prospectively selecting patients for FGFR4 pathway activation."

"We are very encouraged to see early anti-tumor activity in patients with confirmed FGF19 overexpression and consistent evidence of FGFR4 pathway modulation during the dose escalation part of this first-in-human clinical trial," said Andy Boral, M.D., Chief Medical Officer of Blueprint Medicines. "Now that we have demonstrated proof-of-concept, determined the maximum tolerated dose (MTD), and implemented FGF19 biomarker screening globally, we can move rapidly to enroll patients in the expansion part of the study to more fully evaluate the activity of BLU-554 in patients with advanced HCC."

Data from the Ongoing Global Phase 1 Clinical Trial
BLU-554 was evaluated in the dose escalation stage of a Phase 1 clinical trial in patients with advanced HCC. As of the data cutoff date of November 7, 2016, 25 patients had been treated in the dose escalation portion of the Phase 1 clinical trial at five dose levels (ranging from 140 mg once daily (QD) to 900 mg QD), with the majority of patients having previously received sorafenib. The study was designed to retroactively assess patient biopsies for FGFR4 pathway activation after enrollment by evaluating levels of FGF19, the protein that activates FGFR4, using an investigational immunohistochemistry (IHC) assay. 

Prospective screening of patients with the investigational IHC assay was implemented during dose escalation, enabling enrollment of enrichment patients with confirmed FGF19 overexpression which resulted in a larger number than anticipated of biomarker positive patients being enrolled. Blueprint Medicines has initiated the expansion portion of the Phase 1 clinical trial, and enrollment is ongoing.

Pharmacokinetic (PK) data across all dose levels showed rapid oral absorption, a mean half-life of approximately ten hours, and exposure in the expected therapeutic range based on HCC xenograft models.

Pharmacodynamic (PD) data demonstrated FGFR4 pathway inhibition with BLU-554, as evidenced by effects on metabolic pathways downstream of FGFR4, with increases in the bile acid precursor C4, decreases in cholesterol, and feedback upregulation of the ligand FGF19 in blood.

About the Global Phase 1 Clinical Trial for BLU-554 in Advanced HCC
Blueprint Medicines' Phase 1 clinical trial for BLU-554 is designed to evaluate the safety and tolerability of BLU-554 in multiple ascending doses in patients with advanced HCC. Enrollment in the dose-escalation portion of the Phase 1 clinical trial has been completed, and the maximum tolerated dose (MTD) has been determined to be 600 mg QD. Blueprint Medicines has initiated enrollment of the expansion portion of the Phase 1 clinical trial in three defined cohorts at the MTD. The primary objective of the expansion portion of the Phase 1 clinical trial is to continue to evaluate the safety and tolerability of BLU-554. Secondary objectives include assessing clinical activity by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria, as well as evaluating the pharmacokinetics of BLU-554 and pharmacodynamic markers of BLU-554 activity.

The expansion portion of the Phase 1 clinical trial is designed to enroll approximately 45 patients in expansion cohorts, at multiple sites in the United States, European Union and Asia. Please refer to for additional details related to this Phase 1 clinical trial. For more information, please contact the study director for this Phase 1 clinical trial at

About HCC
Liver cancer is the second leading cause of cancer-related deaths worldwide, with HCC accounting for most liver cancers. In the United States, HCC is the fastest rising cause of cancer-related death. Over the past two decades, the incidence of HCC has tripled while the five-year survival rate has remained below 12%. The highest incidence of HCC occurs in regions with endemic hepatitis B virus, including Southeast Asia and sub-Saharan Africa. Treatment options for patients with advanced HCC are limited, with the currently approved first line therapy providing a time to progression that is less than six months and overall survival that is typically less than one year. FGF19 is the ligand that activates FGFR4, which Blueprint Medicines estimates is aberrantly activated in approximately 30% of patients with HCC.  FGF19 and FGFR4 promote hepatocyte proliferation and regulate bile acid homeostasis in the liver.

About BLU-554
BLU‑554 is an orally available, potent, highly selective and irreversible inhibitor of the kinase FGFR4, while sparing the other three FGFR paralogs.  Blueprint Medicines is initially developing BLU-554, an investigational medicine, for the treatment of patients with advanced HCC.  BLU-554 was discovered by Blueprint Medicines' research team, and Blueprint Medicines retains worldwide development and commercialization rights for BLU-554.

About Blueprint Medicines
Blueprint Medicines is developing a new generation of targeted kinase medicines to improve the lives of patients with genomically defined diseases. Its approach is rooted in a deep understanding of the genetic blueprint of cancer and other diseases driven by the abnormal activation of kinases. Blueprint Medicines is advancing three programs in clinical development for subsets of patients with gastrointestinal stromal tumors, hepatocellular carcinoma and systemic mastocytosis, as well as multiple programs in research and preclinical development. For more information, please visit .

Investor Relations:
Kristin Williams, Blueprint Medicines Corporation,

Media Relations:
Rachel Hutman, W2O Group,