CAMBRIDGE, Mass., Dec. 4, 2016 /PRNewswire/ -- Blueprint Medicines
Corporation (NASDAQ: BPMC), a leader in discovering and
developing targeted kinase medicines for patients with genomically
defined diseases, today announced data from its ongoing Phase 1
trial evaluating BLU-285, an investigational medicine for the
treatment of patients with advanced systemic mastocytosis (SM).
Blueprint Medicines is developing BLU-285 as a potent, highly
selective inhibitor of D816V mutant KIT. Approximately 90 to 95
percent of patients with SM are estimated to have the KIT D816V
mutation, the key driver of SM that triggers the abnormal
proliferation and survival of mast cells. The data are being
presented today at the 2016 American Society of Hematology (ASH)
Annual Meeting and Exposition in San
Diego, California.
"Advanced systemic mastocytosis is a rare and severe disease
that shortens life expectancy with a wide range of debilitating
symptoms and organ damage," said Daniel
DeAngelo, M.D., Dana-Farber Cancer Institute, an
investigator on the clinical trial. "We need new treatment options
that address the underlying cause of the disease and can improve
the significant symptoms that impact patients' daily lives. The
objective decreases in mast cell burden and improvements in
symptoms seen in the early data for this Phase 1 study are
encouraging. We believe that BLU-285 has the potential to change
the treatment paradigm for patients affected by advanced systemic
mastocytosis."
"We are excited by these early data demonstrating a favorable
safety profile as well as signs of clinical activity starting at
the first dose level," said Andy
Boral, M.D., Chief Medical Officer at Blueprint Medicines.
"The decreases in bone marrow mast cell burden and serum tryptase,
which are indications of clinical activity, along with the fact
that ten of 12 patients remain on the study, are encouraging and
support the hypothesis that D816V mutant KIT is a driver of this
disease. We look forward to the continued evaluation of our
investigational medicine BLU-285, which we believe has the
potential to be transformative for patients with advanced SM."
Data from the Ongoing Phase 1 Clinical Trial
BLU-285 is currently being evaluated in the dose escalation
portion of a Phase 1 clinical trial in patients with advanced
SM. As of the data cutoff date of November 11, 2016, 12 patients had been treated
at three dose levels (30 mg, 60 mg and 100 mg once daily (QD)). The
median age was 61.5 years (ranging from 39 to 82), and the KIT
D816V mutation has been confirmed in bone marrow or blood from 11
of the 12 patients. Ten of the 12 patients remained on the clinical
trial as of the data cutoff date.
Consistent with preliminary data reported by Blueprint Medicines
from its Phase 1 clinical trial for patients with advanced
gastrointestinal stromal tumors (GIST), BLU-285 demonstrated a
favorable pharmacokinetic profile with a half-life that supports QD
dosing.
Preliminary Safety Data
As of the data cutoff date of November
11, 2016, BLU-285 was observed to be well-tolerated at all
doses. No patients discontinued treatment as a result of an adverse
event (AE), and no Grade 4 or worse treatment-related AEs were
reported. The majority of AEs reported by investigators were Grade
1 or 2, and AEs that occurred in two or more patients were fatigue
(4 patients), anemia (3 patients) and alkaline phosphatase
elevation (3 patients). All three cases of alkaline phosphatase
elevation were Grade 3 but were asymptomatic and transient and
occurred in the absence of transaminase or bilirubin elevations.
The Grade 3 alkaline phosphatase elevations occurred in the three
patients with the highest bone marrow mast cell burden at baseline,
suggesting this may be consistent with a pharmacodynamic effect of
BLU-285 on mast cells in the bone. One of the three cases of
alkaline phosphatase elevation was considered possibly
treatment-related and defined as a dose-limiting toxicity at the 60
mg dose level. All three patients continued treatment with BLU-285
without a dose reduction. A maximum tolerated dose (MTD) has not
been established, and enrollment in the dose escalation portion of
the Phase 1 clinical trial is ongoing.
Preliminary Clinical Activity Data
As of the data cutoff date of November
11, 2016, all 12 patients treated in the first three dose
levels of the dose escalation portion of the clinical trial were
evaluated for signs of clinical activity.
- Investigators observed decreases in bone marrow mast cell
infiltrate (measured by bone marrow biopsy) in six of the eight
patients who had a bone marrow biopsy after starting treatment with
BLU-285. Three of the six patients had a decrease of bone marrow
mast cell infiltrate of more than 50% from baseline, including one
patient with no residual mast cells in the bone marrow.
- Based on measurements at a central laboratory, serum tryptase
decreased in ten of 12 patients. The serum tryptase decrease was
greater than 50% in eight patients.
- The allele burden of D816V mutant KIT decreased within the
first two treatment cycles in five of six patients in circulating
tumor DNA and bone marrow.
- Rash improved in five patients with urticaria pigmentosa from
baseline based on investigator assessments. Urticaria pigmentosa is
an allergy-mediated rash common in SM patients.
- Weight increased in ten patients and albumin increased in 11
patients, suggesting improvements in malabsorption.
- Ten of 12 patients remained on treatment with treatment
duration ranging from 1 month to 8.1 months.
Clinical Development Plans for BLU-285 in SM
Based on the favorable safety profile and encouraging clinical
activity observed to date in the Phase 1 clinical trial for BLU-285
for the treatment of advanced SM, Blueprint Medicines plans to
continue to enroll patients in the dose escalation portion of this
clinical trial until an MTD is reached or a recommended dose is
established. Once a recommended dose for further clinical
evaluation has been determined or an MTD is reached, Blueprint
Medicines plans to open enrollment in expansion cohorts for this
Phase 1 clinical trial for specific subtypes of advanced SM. In
addition, Blueprint Medicines plans to evaluate options to expand
the clinical development of BLU-285 in other KIT-driven diseases,
including possible opportunities for the treatment of indolent SM
and KIT-mutant acute myeloid leukemia, groups of patients in need
of more effective treatments. Blueprint Medicines is also
collaborating with a health research outcomes group to develop a
disease-specific patient reported outcome tool to measure changes
in total symptom burden in advanced SM and indolent SM.
Conference Call Information
Blueprint Medicines will host a conference call and webcast to
review the data presented at the ASH Annual Meeting and Exposition
on Monday, December 5, 2016 beginning
at 8:00 a.m. ET. To participate in
the conference call, please dial 855-728-4793 (domestic) or
503-343-6666 (international) and refer to conference ID 10777452.
An audio webcast of the call will also be available in the
Investors section of Blueprint Medicines' website at
http://ir.blueprintmedicines.com. The archived website will be
available on Blueprint Medicines' website approximately two hours
after the conference call and will be available for 30 days
following the call.
About the Phase 1 Clinical Trial for BLU-285 in Advanced
SM
Blueprint Medicines' Phase 1 clinical trial of BLU-285 for the
treatment of advanced SM is designed to evaluate the safety and
tolerability of BLU-285 in multiple ascending doses in patients
with advanced SM, including aggressive SM (ASM), advanced SM with
an associated hematologic neoplasm (SM‑AHN) and mast cell leukemia
(MCL) with the goal of establishing an MTD or a lower recommended
dose if appropriate. Bone marrow and or blood samples from all
patients are tested for the D816V mutation in KIT. Once the MTD is
reached, or a recommended dose is established, Blueprint Medicines
plans to open expansion cohorts for specific subtypes of advanced
SM. Secondary objectives for this Phase 1 clinical trial include
assessment of the pharmacokinetic profile of BLU-285, assessment of
response rate by the International Working Group Myeloproliferative
Neoplasms Research and Treatment (IWG-MRT) criteria, changes in KIT
D816V mutant allele fractions in bone marrow and circulating tumor
DNA and changes in patient reported outcomes. The Phase 1 clinical
trial is designed to enroll approximately 60 patients, including
approximately 25 patients during dose escalation and approximately
35 additional patients in expansion cohorts, at multiple sites in
the United States and the European
Union. Please refer to www.clinicaltrials.gov for additional
details related to this Phase 1 clinical trial. For more
information, contact the study director for this Phase 1 clinical
trial at studydirector@blueprintmedicines.com.
About SM
There are several forms of SM, including indolent SM and more
advanced forms of SM, which include aggressive SM, SM-AHN and MCL.
SM is characterized by the buildup of mast cells, which are immune
cells that produce histamine and other mediators of the body's
inflammatory and allergic responses. In patients with SM, mast
cells release high levels of these mediators, causing symptoms that
range from mild to life-threatening symptoms, including pain,
nausea, rash, fever, fatigue and anaphylaxis. In patients with
advanced SM, including aggressive SM, SM-AHN and MCL, mast cell
infiltration in bone marrow, liver and other vital organs can
eventually lead to organ dysfunction and lower life expectancy,
with a median overall survival of approximately four years or less.
Patients with indolent SM do not have a lower life expectancy, but
they do suffer from a broad range of acute and chronic symptoms
that can have a significant impact on their quality of life. There
are no approved treatments that target the KIT D816V mutation,
which is the primary driver of disease in approximately 90 to 95
percent of SM patients, and there is a clear need for more
effective therapies for patients with advanced SM and for patients
with indolent SM who have a heavy symptom burden.
About BLU-285
BLU-285 is an orally available, potent and highly selective
inhibitor of D816V mutant KIT. Blueprint Medicines is initially
developing BLU-285, an investigational medicine, for the treatment
of patients with advanced SM and advanced GIST. BLU-285 was
discovered by Blueprint Medicines' research team leveraging its
proprietary compound library, and Blueprint Medicines retains
worldwide development and commercialization rights for BLU-285.
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 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.
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-285; Blueprint Medicines' ability to implement its clinical
development plans for BLU-285 for the treatment of advanced SM;
Blueprint Medicines' ability to enroll patients in its ongoing
Phase 1 clinical trial for BLU-285 in advanced SM; 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
product candidates, including BLU-285 and BLU-554; Blueprint
Medicines' advancement of multiple early-stage efforts; Blueprint
Medicines' ability to successfully demonstrate the efficacy and
safety of its drug product candidates; the preclinical and clinical
results for Blueprint Medicines' drug product candidates, which may
not support further development of such drug product candidates;
and actions of regulatory agencies, which may affect the
initiation, timing and progress of clinical trials; Blueprint
Medicines' ability to develop and commercialize companion
diagnostics for its current and future drug candidates, including
companion diagnostics for BLU-554 with Ventana Medical Systems,
Inc. and for BLU-285 with QIAGEN Manchester Limited; and the
success of Blueprint Medicines' rare genetic disease collaboration
with Alexion Pharma Holding and its 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
September 30, 2016, as filed with the
Securities and Exchange Commission (SEC) on November 10, 2016, 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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