CAMBRIDGE, Mass., Sept. 10, 2017 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC), a leader in discovering and
developing targeted kinase medicines for patients with genomically
defined diseases, today announced updated data from its ongoing
Phase 1 clinical trial of BLU-554, a potent and highly selective
inhibitor of fibroblast growth factor receptor 4 (FGFR4) for the
treatment of patients with advanced hepatocellular carcinoma (HCC).
As of a data cutoff date of August 18,
2017, BLU-554 demonstrated a 16 percent objective response
rate (ORR) in patients with FGFR4-driven HCC. In addition, 49
percent of patients with FGFR4-driven HCC had radiographic tumor
reduction. BLU-554 was well-tolerated and most adverse events (AEs)
reported by investigators were Grade 1 or 2. The data will be
presented today in an oral presentation at the European Society for
Medical Oncology (ESMO) 2017 Congress in Madrid, Spain.
"Patients with hepatocellular carcinoma face a very poor
prognosis with few therapeutic options," said Richard Kim, M.D., Associate Professor, Moffit
Cancer Center, an investigator for the study. "The new BLU-554 data
announced today show that in heavily pre-treated patients, BLU-554
demonstrated encouraging clinical activity, with approximately half
of patients with FGFR4-driven HCC having tumor shrinkage.
These data compare well to historical data for currently approved
agents showing response rates of approximately 10 percent or less,
and BLU-554 has the potential to change the treatment paradigm for
patients with FGFR4-driven HCC."
"We are encouraged by the updated BLU-554 Phase 1 data presented
at ESMO, which build on our prior clinical experience and suggest
that BLU-554 may offer meaningful benefit to patients with
FGFR4-driven HCC," said Andy Boral,
M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "These
data speak to BLU-554's potential as the first biomarker-driven
targeted therapy for liver cancer. The higher frequency of tumor
reduction in patients with FGFR4-driven HCC confirm the importance
of aberrantly activated FGFR4 signaling in driving a subset of
patients' disease and demonstrate BLU-554's ability to modulate the
FGFR4 pathway."
Updated Data from the Ongoing Phase 1 Clinical Trial
BLU-554 is currently being evaluated in a Phase 1 clinical trial
in patients with advanced HCC. Following the completion of the dose
escalation portion of the trial and determination of the maximum
tolerated dose (MTD) of 600 mg once daily (QD), Blueprint Medicines
initiated the expansion portion of the trial.
As of the data cutoff of August 18,
2017, 77 patients had been treated with BLU-554 in the dose
escalation and expansion portions of the Phase 1 clinical trial at
five dose levels (ranging from 140 mg QD to 900 mg QD), including
44 patients with FGFR4-driven HCC. FGFR4-driven HCC was defined as
at least one percent tumor expression of FGF19, the FGFR4 ligand,
as measured by an immunohistochemistry (IHC) assay. In general, the
enrolled population was heavily pretreated: 82 percent received
prior tyrosine kinase inhibitor (TKI) treatment, 23 percent
received prior immunotherapy, and 91 percent received prior
systemic therapy.
Pharmacokinetic (PK) analysis demonstrated rapid oral absorption
across all dose levels, with a mean half-life of approximately 17
hours and exposure in the expected therapeutic range based on HCC
xenograft models. Collectively, these data support a once-daily
dosing regimen.
Safety Data
As of the data cutoff of August 18,
2017, the majority of AEs reported by investigators were
Grade 1 or 2. Across all grades, the most common AEs reported by
investigators related to BLU-554 included diarrhea (71%), nausea
(42%), vomiting (36%), transaminase elevation (AST 34% and ALT 32%)
and fatigue (29%). Grade 3 or higher AEs related to BLU-554
occurring in five or more patients included anemia, diarrhea and
transaminase elevation (AST and ALT). Among all 77 patients
treated with BLU-554, 58 patients discontinued treatment with
BLU-554, including 42 patients due to disease progression, 11
patients due to treatment-related AEs, three patients who withdrew
consent and two patients due to the investigator's decision.
Clinical Activity Data
As of the data cutoff of August 18,
2017, 67 patients were evaluable for response assessment. An
additional 10 patients were treated with BLU-554 as of the data
cutoff date but were not evaluable for response assessment.
Response was assessed using the Response Evaluation Criteria
In Solid Tumors (RECIST) version 1.1.
In patients with FGFR4-driven HCC (n=38), the data showed an ORR
of 16 percent (95 percent confidence interval 6-31 percent). In
addition, 49 percent of patients had radiographic tumor reduction,
and clinical activity was observed regardless of disease etiology
or geography. As of the data cutoff date:
- One patient had an unconfirmed complete response.
- Five patients had a partial response, with four confirmed and
one unconfirmed.
- An additional 20 patients had stable disease, representing a
disease control rate of 68 percent.
- No responses were observed in patients without FGFR4 pathway
activation (n=29).
Among all 77 patients treated with BLU-554, 19 remained on
treatment as of the data cutoff date, including 15 patients with
FGFR4-driven HCC. Median progression free survival was 3.7 months
among patients with FGFR4-driven HCC.
In addition, five TKI-naïve patients with FGFR4-driven HCC were
evaluable for response assessment as of the data cutoff date.
Within this group, preliminary evidence of prolonged disease
control was observed. Two TKI-naïve patients remain on treatment as
of the data cutoff with a duration of treatment of 11.4 months and
12.3 months, respectively.
Clinical Development Plans for BLU-554
Blueprint Medicines plans to continue to enroll and follow the
cohort of patients with FGFR4-driven HCC in the ongoing Phase 1
clinical trial to further evaluate the safety and clinical activity
of BLU-554 in this population. In addition, the Company plans to
initiate an additional cohort in this clinical trial in the first
quarter of 2018 to evaluate BLU-554 in TKI-naïve patients with
FGFR4-driven HCC. Blueprint Medicines also plans to explore
opportunities to conduct a clinical trial to evaluate BLU-554 in
combination with an immune checkpoint inhibitor.
Conference Call Information
Blueprint Medicines will host a conference call and webcast on
Monday, September 11, 2017 at
7:00 a.m. ET (1:00 p.m. CET) to discuss the BLU-554 clinical
data presented at ESMO. To participate in the conference call,
please dial 1-855-728-4793 (domestic) or 1-503-343-6666
(international) and refer to conference ID 73748225. A live webcast
of the presentation will also be available under "Events &
Presentations" in the Investors section of Blueprint Medicines'
website at http://ir.blueprintmedicines.com/. The archived webcast
will be available on Blueprint Medicines' website approximately two
hours after the event concludes and will be available for 30 days
following the event.
About the 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. The
dose-escalation portion of the Phase 1 clinical trial was
completed, and the maximum tolerated dose (MTD) was determined to
be 600 mg QD. Blueprint Medicines is currently enrolling
the expansion portion of the Phase 1 clinical trial 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, as
well as evaluating the PK of BLU-554 and pharmacodynamic markers of
BLU-554 activity. The expansion portion of the Phase 1 clinical
trial is designed to enroll approximately 60 patients in expansion
cohorts with QD dosing, at multiple sites in the United
States, European Union and Asia. Please refer
to www.clinicaltrials.gov 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 studydirector@blueprintmedicines.com.
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 percent. 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 typically providing time
to progression of less than six months and overall survival of less
than one year. FGF19 is the ligand that activates FGFR4, a receptor
that promotes hepatocyte proliferation and regulates bile acid
homeostasis in the liver. Blueprint Medicines estimates that
approximately 30 percent of patients with HCC have tumors with
aberrantly activated FGFR4 signaling.
About BLU-554
BLU-554 is an orally available, potent, irreversible inhibitor
of FGFR4 discovered and being developed by Blueprint Medicines.
BLU-554 was specifically designed by Blueprint Medicines to inhibit
FGFR4 with exquisite selectivity, thereby sparing the paralogs
FGFR1, FGFR2 and FGFR3. Blueprint Medicines is developing BLU-554,
an investigational medicine, for the treatment of patients with
FGFR4-driven HCC. The Company retains worldwide development and
commercialization rights for BLU-554. In addition, Blueprint
Medicines and Ventana Medical Systems, Inc. are developing an IHC
assay as a companion diagnostic test for use with BLU-554 to
identify HCC patients with aberrantly active FGFR4 signaling as
indicated by FGF19 protein overexpression.
About Blueprint Medicines
Blueprint Medicines is developing a new generation of
targeted and potent 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 four programs
in clinical development for subsets of patients with
gastrointestinal stromal tumors, hepatocellular carcinoma, systemic
mastocytosis, non-small cell lung cancer, medullary thyroid cancer
and other advanced solid tumors, as well as multiple programs in
research and preclinical development. For more information, please
visit www.blueprintmedicines.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, statements
regarding plans and timelines for the clinical development of
BLU-554, including plans and timelines for clinical trials
evaluating BLU-554 in TKI-naïve patients with FGFR4-driven HCC or
BLU-554 in combination with an immune checkpoint inhibitor;
Blueprint Medicines' ability to implement its clinical development
plans for BLU-554 in advanced HCC; Blueprint Medicines' ability to
enroll patients in its ongoing Phase 1 clinical trial for BLU-554
in advanced HCC; and Blueprint Medicines' strategy, business plans
and focus. The words "may," "will," "could," "would," "should,"
"expect," "plan," "anticipate," "intend," "believe," "estimate,"
"predict," "project," "potential," "continue," "target" and similar
expressions are intended to identify forward-looking statements,
although not all forward-looking statements contain these
identifying words. Any forward-looking statements in this press
release are based on management's current expectations and beliefs
and are subject to a number of risks, uncertainties and important
factors that may cause actual events or results to differ
materially from those expressed or implied by any forward-looking
statements contained in this press release, including, without
limitation, risks and uncertainties related to the delay of any
current or planned clinical trials or the development of Blueprint
Medicines' drug candidates, including BLU-285, BLU-554 and BLU-667;
Blueprint Medicines' advancement of multiple early-stage efforts;
Blueprint Medicines' ability to successfully demonstrate the safety
and efficacy of its drug candidates; the preclinical and clinical
results for Blueprint Medicines' drug candidates, which may not
support further development of such drug candidates; and actions of
the FDA or other regulatory agencies, which may affect the
initiation, timing and progress of clinical trials; Blueprint
Medicines' ability to develop and commercialize companion
diagnostic tests for its current and future drug candidates,
including companion diagnostic tests for BLU-554 with Ventana
Medical Systems, Inc. and for BLU-285 with QIAGEN Manchester
Limited; and the success of Blueprint Medicines' cancer
immunotherapy collaboration with F. Hoffmann-La Roche Ltd and
Hoffmann-La Roche Inc. These and other risks and uncertainties are
described in greater detail in the section entitled "Risk Factors"
in Blueprint Medicines' Quarterly Report on Form 10-Q for the
quarter ended June 30, 2017, as filed
with the Securities and Exchange Commission (SEC) on August 2, 2017, and other filings that Blueprint
Medicines may make with the SEC in the future. Any forward-looking
statements contained in this press release represent Blueprint
Medicines' views only as of the date hereof and should not be
relied upon as representing its views as of any subsequent date.
Blueprint Medicines explicitly disclaims any obligation to update
any forward-looking statements.
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