CAMBRIDGE, Mass., Dec. 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 new data from its ongoing Phase 1
clinical trial of avapritinib (formerly known as BLU-285), a potent
and highly selective KIT and PDGFRα inhibitor in development for
patients with advanced systemic mastocytosis (SM). The new data
from the dose escalation portion of the Phase 1 trial showed strong
clinical activity regardless of advanced SM subtype, prior
treatment with midostaurin or the presence of additional
mutations.
As of the data cutoff date of October 4,
2017, the data showed an overall response rate (ORR) of 72
percent and a disease control rate (DCR) of 100 percent in patients
evaluable for response, based on the International Working
Group-Myeloproliferative Neoplasms Research and Treatment and
European Competence Network on Mastocytosis (IWG-MRT-ECNM)
consensus criteria. As of the data cutoff date, avapritinib was
well-tolerated and most adverse events (AEs) reported by
investigators were Grade 1 or 2. In addition, there were no
discontinuations due to treatment-related adverse events, and 30 of
32 patients remained on treatment with a median treatment duration
of nine months. The data will be presented today in an oral
presentation during the Plenary Scientific Session at the
59th American Society of Hematology Annual Meeting and
Exposition (ASH) in Atlanta,
Georgia.
Based on these data, Blueprint Medicines plans to engage global
regulatory authorities in the first half of 2018 to obtain input on
registration pathways for avapritinib in patients with advanced SM
and patients with indolent and smoldering SM. Subject to regulatory
feedback, the Company anticipates initiating a
registration-enabling clinical trial of avapritinib in patients
with advanced SM in the first half of 2018 and a dose escalation
and proof-of-concept clinical trial of avapritinib in patients with
indolent and smoldering SM in the second half of 2018. In addition,
Blueprint Medicines continues to enroll patients in the expansion
portion of the ongoing Phase 1 clinical trial in patients with
advanced SM with the goal of generating additional data in
2018.
"The new clinical trial results for avapritinib reported at the
ASH plenary scientific session represent an exciting milestone for
the systemic mastocytosis community. The data showed a remarkably
high response rate and a favorable tolerability profile, suggesting
avapritinib has the potential to transform the treatment of this
devastating rare disease," said Daniel J.
DeAngelo, M.D., Ph.D., Director of Clinical and
Translational Research, Adult Leukemia at Dana-Farber Cancer
Institute, Associate Professor of Medicine at Harvard Medical School, and an investigator on the
Phase 1 trial. "The data also provide strong evidence that
selective inhibition of D816V mutant KIT, a disease-driver present
in nearly all patients across the spectrum of SM, is a potentially
important treatment strategy that may offer patients improved
outcomes. These data strongly support continued development of
avapritinib in a broad population of patients with SM."
"We are extremely encouraged by the tolerability and clinical
activity of avapritinib observed to date, which increase our
confidence and reinforce our commitment to rapidly advance its
development across the spectrum of SM," said Andy Boral, M.D., Ph.D., Chief Medical Officer
at Blueprint Medicines. "We look forward to engaging with global
regulatory authorities in the first half of 2018 to obtain feedback
on a potential registration pathway. In addition, based on data
showing a favorable tolerability profile and strong clinical
activity from the lowest dose levels tested, we plan to expand our
clinical development program to address the full spectrum of SM,
including advanced, smoldering and indolent forms of the disease,
over the course of 2018."
New Data from the Ongoing Phase 1 Clinical Trial of
Avapritinib in Advanced SM
As of the data cutoff date of October 4,
2017, 32 patients had been treated with avapritinib in the
dose escalation portion of the Phase 1 clinical trial at seven dose
levels (ranging from 30 mg to 400 mg once daily (QD)), including 17
patients with aggressive SM (ASM), nine patients with advanced SM
with an associated hematologic neoplasm (SM-AHN) and three patients
with mast cell leukemia (MCL). The KIT D816V mutation was confirmed
in 28 patients. Overall, 22 patients (69 percent) previously
received anti-neoplastic therapy, including four patients (13
percent) who previously received midostaurin.
Based on pharmacokinetic (PK) data, avapritinib demonstrated a
mean half-life of greater than 20 hours, supporting a QD dosing
regimen.
Blueprint Medicines has selected 300 mg QD as the recommended
part two dose (RP2D) for the expansion portion of this trial, which
was initiated in the second quarter of 2017. A maximum tolerated
dose of avapritinib in advanced SM was not determined.
Safety Data
As of the data cutoff date, avapritinib was generally
well-tolerated. Most AEs reported by investigators were Grade 1 or
2. The most common treatment-emergent AEs reported by investigators
(≥20 percent) across all grades included periorbital edema (59
percent), fatigue (41 percent), peripheral edema (34 percent),
nausea (28 percent), anemia (28 percent), thrombocytopenia (28
percent), abdominal pain, diarrhea, respiratory tract infection,
dizziness and headache (22 percent each). Investigators reported
treatment-related Grade ≥3 AEs in 16 patients (50 percent), with
only one treatment-related Grade ≥3 AE occurring in more than 10
percent of patients (neutropenia, 13 percent).
No patients discontinued treatment due to a treatment-related
AE. Two patients discontinued treatment with avapritinib, including
one patient with ASM who had progressive disease with
transformation to acute myeloid leukemia and one patient with
SM-AHN and no identified KIT mutation (i.e., wild-type KIT).
Overall, 30 of 32 patients enrolled in the dose escalation portion
of the trial remained on treatment as of the data cutoff date, with
a median duration of 9 months (range 4 to 19 months).
Clinical Activity Data
IWG-MRT-ECNM Response Assessment
The IWG-MRT-ECNM criteria comprise a rigorous assessment of
clinical response in patients with advanced SM. These criteria
include objective measures of bone marrow mast cell burden, serum
tryptase and improvement in organ damage as measured by a clinical
improvement (CI) finding.
As of the data cutoff date, 18 patients had advanced SM and were
evaluable for response by the IWG-MRT-ECNM criteria.
Across all 18 evaluable patients with advanced SM, the data
showed an ORR of 72 percent and a complete response (CR) + partial
response (PR) rate of 56 percent. A detailed summary of response
data is provided below.
Avapritinib
in Patients with Advanced SM; Assessment of Response per
IWG-MRT-ECNM Criteria
|
Best Response,
Number of Patients (%)*
|
ASM
(n=7)
|
SM-AHN
(n=8)
|
MCL
(n=3)
|
Overall
(n=18)
|
CR
|
2 (29%)
|
0
|
0
|
2 (11%)
|
PR
|
3 (43%)
|
4 (50%)
|
1 (33%)
|
8 (44%)
|
Clinical improvement
(CI)
|
1 (14%)
|
1 (13%)
|
1 (33%)
|
3 (17%)
|
Stable disease
(SD)
|
1 (14%)
|
3 (38%)
|
1 (33%)
|
5 (28%)
|
ORR (CR + PR +
CI)
|
6 (86%)
|
5 (63%)
|
2 (67%)
|
13 (72%)
|
CR + PR
|
5 (71%)
|
4 (50%)
|
1 (33%)
|
10 (56%)
|
*Responses pending
confirmation: ASM: 2 CR; SM-AHN: 3 PR
|
Additional Clinical Assessments
In addition, results from individual components of the
IWG-MRT-ECNM were reported as of the data cutoff date. Clinically
meaningful improvements were observed in all evaluable patients,
across all subtypes of advanced SM and at all avapritinib dose
levels evaluated.
- All 32 enrolled patients had decreases in serum tryptase
greater than 50 percent.
- All 25 patients who had bone marrow mast cell infiltrate of at
least 5 percent at baseline (measured by bone marrow biopsy) showed
decreases in bone marrow mast cell burden. In this group, 21
patients had at least a 50 percent decrease, and 15 patients
achieved a CR for bone marrow mast cell burden.
- All 25 patients with centrally reviewed radiographic scans
showed decreases in spleen volume. In this group, 14 patients had
at least a 35 percent reduction in spleen volume.
In addition, rash improved in 13 of 15 patients with urticaria
pigmentosa at baseline, based on investigator assessments.
Urticaria pigmentosa is an allergy-mediated rash common in SM
patients.
Conference Call Information
Blueprint Medicines will host a conference call and webcast
on Monday, December 11, 2017 at 6:00 a.m. ET to
discuss the avapritinib (BLU-285) clinical data presented at ASH
and provide an update on its broader preclinical and clinical
pipeline.
To participate in the conference call, please dial
1-855-728-4793 (domestic) or 1-503-343-6666 (international) and
refer to conference ID 4072589. A live webcast will be available
under "Events and Presentations" in the Investors section
of Blueprint Medicines' website
at http://ir.blueprintmedicines.com. A replay of the webcast
will be available approximately two hours after the conference call
and will be available for 30 days following the call.
About the Phase 1 Clinical Trial for Avapritinib (BLU-285) in
Advanced SM
The Phase 1 clinical trial of avapritinib is designed to
evaluate the safety and tolerability of avapritinib in adults with
advanced SM. The trial consists of two parts, a dose escalation
portion and an expansion portion. The dose escalation portion is
complete, and Blueprint Medicines selected 300 mg QD as the RP2D
for the dose expansion portion of the trial. The expansion portion
is actively enrolling patients in three defined cohorts for
specific subtypes of advanced SM, including ASM, SM‑AHN and MCL.
Trial objectives include assessing safety and tolerability,
response per IWG-MRT-ECNM criteria and additional clinical outcome
measures of mast cell burden, organ function and disease symptoms.
The Phase 1 clinical trial is designed to enroll approximately 60
patients, including approximately 35 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, smoldering
SM and more advanced forms of SM, which include ASM, SM-AHN and
MCL. SM is a hematological clonal disorder 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
ASM, SM-AHN and MCL, mast cell infiltration in bone marrow, liver
and other vital organs can eventually lead to organ dysfunction and
shortened life expectancy, with a median overall survival of three
to five years. Patients with indolent SM do not have a shortened
life expectancy, but they do suffer from a broad range of acute and
chronic symptoms that negatively impact their quality of life.
There are no approved treatments that target D816V mutant KIT,
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 Avapritinib (BLU-285)
Avapritinib is an orally available, potent and highly selective
inhibitor of KIT and PDGFRα. Preclinical data have shown that
avapritinib is active across a broad spectrum of KIT and PDGFRα
mutations, including KIT D816V, PDGFRα D842V and KIT exon 17
mutations for which there are limited or no effective treatment
options. Blueprint Medicines is initially developing avapritinib,
an investigational medicine, for the treatment of patients with
advanced gastrointestinal stromal tumors (GIST) and advanced SM.
Avapritinib was discovered by Blueprint Medicines' research team
leveraging its proprietary compound library, and the Company
retains worldwide development and commercialization rights for
avapritinib.
In June 2017, avapritinib received
Breakthrough Therapy Designation from the U.S. Food and Drug
Administration (FDA) for the treatment of patients with
unresectable or metastatic GIST harboring the PDGFRα D842V
mutation. The FDA's Breakthrough Therapy Designation is intended to
expedite the development and review of a drug candidate intended to
treat a serious or life-threatening disease or condition, when
preliminary clinical evidence indicates that the drug candidate may
demonstrate substantial improvement over existing therapies on one
or more clinically significant endpoints. Previously, the FDA
granted orphan drug designation to avapritinib for the treatment of
GIST and mastocytosis. The FDA also granted Fast Track designation
to avapritinib for the treatment of patients with unresectable or
metastatic GIST that progressed following treatment with imatinib
and a second tyrosine kinase inhibitor and for the treatment of
patients with unresectable or metastatic GIST in patients with the
PDGFRα D842V mutation regardless of prior therapy. In addition, the
European Commission has granted orphan drug designation to
avapritinib for the treatment of GIST.
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
avapritinib (formerly known as BLU-285), including plans and
timelines for initiating a registration-enabling clinical trial for
avapritinib in patients with advanced SM and a dose escalation and
proof-of-concept clinical trial for avapritinib in patients with
indolent and smoldering SM; Blueprint Medicines' ability to
implement its clinical development plans for avapritinib in
advanced SM; expectations regarding current and future interactions
with global regulatory authorities, including the FDA, and the
impact of Breakthrough Therapy Designation on the development of
avapritinib; 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
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 for FGFR4-driven HCC, BLU-285 for PDGFRα
D842V-driven GIST and BLU-667 for RET-driven non-small cell lung
cancer; 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 September 30, 2017, as
filed with the Securities and Exchange Commission (SEC) on
October 31, 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.
SOURCE Blueprint Medicines Corporation