CAMBRIDGE, Mass.—In a report released this March, Blueprint Medicines Corp., a company dedicated to discovering and developing targeted kinase medicines for patients with genomically defined diseases, detailed positive scientific and financial results for 2016. Included in that report were encouraging data on two new kinase-inhibiting therapies currently in clinical trials, FDA approval for a third such therapy and a successful public offering of stock.
“2016 was a transformative year for Blueprint Medicines in which we achieved all of our corporate goals, including a number of important milestones,” said Jeff Albers, CEO of Blueprint Medicines, in a media release.
At the core of the report was news of the presentation at bioscience conferences of proof-of-concept data for two kinase-inhibiting therapies in clinical trials involving three patient populations. At the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in November 2016, Blueprint presented data from its ongoing Phase 1 clinical trial for BLU-554 as a treatment for hepatocellular carcinoma (HCC). BLU-554 was designed to inhibit the kinase fibroblast growth factor receptor 4 (FGFR4), while sparing other members of the FGFR family and other kinases. The company asserts that this may offer the first biomarker-driven targeted therapy for patients with advanced HCC, a disease that accounts for most liver cancers, which are the second leading cause of cancer-related deaths worldwide.
Scientists at Blueprint estimate that 30 percent of patients with HCC have tumors which aberrantly activated FGFR4 signaling. The data presented showed encouraging single-agent clinical activity of BLU-554 in heavily pretreated advanced HCC patients as well as pharmacodynamic evidence of FGFR4 pathway modulation. The maximum tolerated dose (MTD) was determined to be 600 mg once daily, and enrollment in the dose-expansion portion of this clinical trial is ongoing at the MTD.
Another kinase-inhibiting therapy, BLU-285, was designed to target mutations in the PDGFRα and KIT genes, and is being developed to treat two rare diseases. In an oral presentation at the same EORTC-NCI-AACR meeting, Blueprint presented data from its ongoing Phase 1 clinical trial for BLU-285 in two patient populations with metastatic and treatment-resistant gastrointestinal stromal tumors (GIST), a rare disease that is a sarcoma of the gastrointestinal tract.
The data showed that BLU-285 was well tolerated by patients and demonstrated significant preliminary clinical activity, including tumor reductions in patients with PDGFRα-driven GIST beginning with the first dose level and tumor reductions at higher dose levels in refractory patients with KIT-driven GIST. An MTD of 400 mg once daily was established, and enrollment in the escalation portion of this clinical trial has been completed.
BLU-285 was also designed for those suffering from systemic mastocytosis (SM), a rare and severe blood disease characterized by abnormal accumulation of mast cells. In this case, the target is the KIT D816V mutant, the primary driver of disease in 90 to 95 percent of SM patients. At the 2016 American Society of Hematology Annual Meeting in December, Blueprint Medicines presented data from its ongoing Phase 1 clinical trial for BLU-285 in patients with advanced SM. The data showed early clinical activity for BLU-285 in that patient set, beginning at the lowest dose levels, and marked decreases in objective measures of mast cell burden. While the data also showed that BLU-285 was well tolerated, with no patients discontinuing treatment due to adverse events, patients were still being enrolled for the dose-escalation portion of those clinical trials.
Discussing these early results in a conference call, Dr. Andy Boral, chief medical officer of Blueprint Medicines, seemed encouraged. “These data,” he remarked, “demonstrate that targeting the D816 genetic driver with a highly potent and selective inhibitor like BLU-285 has the potential to address not only the symptoms of the disease, but also its underlying cause.”
Blueprint’s March report also included news of the January announcement that it had won FDA approval of its Investigational New Drug application for a third therapy, BLU-667. BLU-667 is a selective inhibitor of RET activating fusions, mutations and predicted resistance mutations, and was designed for patients with non-small cell lung cancer, medullary thyroid cancer and other advanced solid tumors that harbor a RET alteration.
In a subsequent release in March, the company also announced that it had dosed the first patient in a Phase 1 clinical trial of BLU-667. “RET fusions and mutations are recognized as important drivers in multiple cancers,” Boral said in that release, “but existing multi-kinase inhibitors with RET activity do not provide sufficient, durable benefit for patients with RET alterations. BLU-667 is being developed to potently inhibit RET, and simultaneously prevent the development of on-target resistance, which we believe will provide more lasting clinical benefit and prevent or delay disease recurrence. We look forward to working with patients and physicians to explore BLU-667’s potential.”
Blueprint Medicines anticipates providing updated data from all these clinical trials in 2017.