-- AYVAKIT showed a superior mean change in
total symptom score (p=0.003), compared to placebo plus best
available care --
-- Highly significant reductions across all
objective measures of mast cell burden reinforce the disease
modifying activity of AYVAKIT --
-- AYVAKIT had a favorable safety profile
compared to the control arm, supporting potential for long-term
treatment --
-- Plan to submit supplemental new drug
application to FDA in fourth quarter of 2022 --
-- Blueprint Medicines to host investor
conference call and webcast today at 8:00
a.m. ET --
CAMBRIDGE, Mass., Aug. 17,
2022 /PRNewswire/ -- Blueprint Medicines Corporation
(NASDAQ: BPMC) today announced positive top-line results from the
registrational Part 2 of the PIONEER clinical trial of
AYVAKIT® (avapritinib) in patients with non-advanced
systemic mastocytosis (SM) demonstrating clinically meaningful and
highly significant improvements across the primary and all key
secondary endpoints, including patient-reported symptoms and
objective measures of mast cell burden. Based on these top-line
data, Blueprint Medicines plans to submit a supplemental new drug
application (sNDA) to the U.S. Food and Drug Administration (FDA)
for AYVAKIT in non-advanced SM in the fourth quarter of 2022, with
a subsequent submission of a type II variation marketing
authorization application to the European Medicines Agency (EMA)
anticipated in 2023. In addition, Blueprint Medicines plans to
present detailed data from the PIONEER trial at an upcoming medical
meeting.
The trial, which was designed to assess AYVAKIT plus best
available care versus placebo plus best available care (control
arm), achieved its primary endpoint with a highly significant
difference in the mean change in total symptom score (TSS) at 24
weeks (p=0.003). TSS was assessed by the Indolent SM Symptom
Assessment Form (ISM-SAF). The AYVAKIT arm had a reduction of 15.6
points in mean TSS at 24 weeks, which continued to deepen to 20.2
points at 48 weeks in patients who rolled over to the Part 3
open-label extension study. At 24 weeks, the control arm had a
reduction of 9.2 points in mean TSS. In addition, the PIONEER trial
met all key secondary endpoints, including significant improvements
across all measures of mast cell burden. More than half of
AYVAKIT-treated patients had a ≥50 percent reduction of serum
tryptase, compared to no patients in the control arm (53.9% vs. 0%;
p<0.0001). AYVAKIT was well-tolerated and had a favorable safety
profile, and 96.5 percent of AYVAKIT-treated patients completed 24
weeks of therapy, compared to 93.0 percent for the control arm.
Overall, 0.7 percent of patients in the AYVAKIT arm and no patients
in the control arm discontinued due to treatment-related adverse
events.
"As a physician and clinical researcher who has been treating
non-advanced systemic mastocytosis patients for over 25 years, I
have been awaiting a therapy that decreases the abnormal mast cell
burden and activation, improves a wide range of symptoms, and
ultimately provides an improved quality of life to patients," said
Mariana Castells, M.D., Ph.D.,
Director, Mastocytosis Center, Brigham and Women's Hospital, and an
investigator on the PIONEER trial. "For patients with non-advanced
SM, PIONEER is the first study to show significant clinical
improvements over best available care across patient-reported
symptoms and objective measures of disease, with a safety and
tolerability profile supporting chronic treatment. The trial
results suggest that if approved, AYVAKIT would represent a
practice-changing treatment, enabling important clinical benefits
for a broad range of patients with non-advanced SM."
"The PIONEER results showcase Blueprint Medicines' dedication to
advancing the promise of precision therapy for patients with
significant medical needs," said Becker Hewes, M.D., Chief Medical
Officer at Blueprint Medicines. "AYVAKIT has the potential to be
the first approved medicine for non-advanced SM, and the only
treatment that would address the genetic root cause across advanced
and non-advanced forms of the disease. Today's milestone represents
a watershed moment for the systemic mastocytosis community and
Blueprint Medicines, capping a decade of collaboration with
clinicians, advocates and patients to transform standards of care,
and to deepen the understanding of this disease and its impact on
various aspects of patients' lives."
AYVAKIT was designed to potently and selectively inhibit D816V
mutant KIT, the driver of SM in about 95 percent of cases. SM often
leads to debilitating skin, gastrointestinal, neurocognitive and
other systemic symptoms, such as life-threatening anaphylaxis.
"Non-advanced systemic mastocytosis is a lifelong disease with
severe physical, emotional and social impacts that profoundly
reduce patients' quality of life," said Lauren Denton, Executive Director of The Mast
Cell Disease Society. "Patients with SM continue to be challenged
by efforts to avoid various triggers of everyday life while also
managing complex therapies. The PIONEER clinical trial results
offer hope to these patients and help pave the way for new
innovation in treatment."
"These new data are the culmination of a dedicated long-term
collaboration and shared 'patients first' core value between
Blueprint Medicines and The Mast Cell Disease Society. We are
excited by these results and further energized to work together
with these exceptional investigators to transform the lives of
patients, offering them a better quality of life and the gift of
time," said Valerie Slee, Board
Chair of The Mast Cell Disease Society.
Top-line Data from the PIONEER Trial
Part 2 of the registrational PIONEER trial was designed to
evaluate the efficacy and safety of AYVAKIT (25 mg once-daily
dosing; N=141) versus control (N=71) over 24 weeks of treatment.
Eligibility criteria include an indolent SM diagnosis confirmed by
central pathology review, and moderate-to-severe symptom burden
despite an optimized regimen of best available care. Patients were
able to continue symptom-directed therapies while receiving AYVAKIT
or placebo. Results were reported as of a data cutoff date of
June 23, 2022.
Baseline data, including mean TSS, were consistent with Part 1
of the trial. The PIONEER study achieved its primary endpoint and
all key secondary endpoints, with AYVAKIT showing highly
significant improvements in patient-reported symptoms and objective
measures of disease burden.
Clinical Outcome
Measures: AYVAKIT Arm vs. Control Arm
|
P-valuea
|
Primary
Endpoint
|
Mean Change in
TSS
|
p=0.003
|
Secondary
Endpointsb
|
≥30% Reduction in Mean
TSS
|
p=0.009
|
≥50% Reduction in Mean
TSS
|
p=0.005
|
Mean Change in Most
Severe Symptom Score
|
p=0.015
|
≥50% Reduction in Serum
Tryptase
|
p<0.0001
|
≥50% Reduction in KIT
D816V Variant Allele Fraction
|
p<0.0001
|
≥50% Reduction in Bone
Marrow Mast Cell Aggregates
|
p<0.0001
|
a One-sided p-value <0.025
indicates statistical significance.
|
b For
secondary endpoints, reductions in TSS and objective measures of
mast cell burden represent
proportion of patients with ≥30% and ≥50% reductions. All endpoints
are key secondary endpoints,
except for mean change in most severe symptom score, which is an
additional secondary endpoint.
|
AYVAKIT had a favorable safety profile compared to the control
arm. The rate of adverse events (AEs) was 90.8 percent in the
AYVAKIT arm and 93.0 percent in the control arm. Serious AEs
occurred in 5.0 percent of AYVAKIT-treated patients, compared to
11.3 percent of patients in the control arm. Discontinuations due
to treatment-related AEs occurred in 0.7 percent of AYVAKIT-treated
patients and 0 percent of patients in the placebo arm. The
AYVAKIT arm had a lower rate of cognitive AEs than the control arm
(2.8% AYVAKIT vs. 4.2% control), and there were no intracranial
bleeding events. Treatment-related AEs reported in at least three
patients in either arm and at least 5 percent of AYVAKIT-treated
patients included headache (7.8% AYVAKIT vs. 9.9% control), nausea
(6.4% AYVAKIT vs 8.5% control), peripheral edema (6.4% AYVAKIT vs.
1.4% control) and periorbital edema (6.4% AYVAKIT vs. 2.8%
control). In the AYVAKIT arm, 93.0 percent of edema AEs were Grade
1 and the remainder were Grade 2.
Conference Call Information
Blueprint Medicines will host a live conference call and webcast
at 8:00 a.m. ET today to discuss the
top-line data from the PIONEER trial. The conference call may be
accessed by dialing 844-200-6205 (domestic) or 929-526-1599
(international), and referring to conference ID 806215. A webcast
of the call will also be available under "Events and Presentations"
in the Investors & Media section of the Blueprint Medicines
website at http://ir.blueprintmedicines.com/. The archived webcast
will be available on the Blueprint Medicines website approximately
two hours after the conference call and will be available for 30
days following the call.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA
for the treatment of adults with Advanced SM, including aggressive
SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and
mast cell leukemia (MCL), and adults with unresectable or
metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA
exon 18 mutation, including PDGFRA D842V mutations. For more
information, visit AYVAKIT.com. This medicine is approved in
Europe (AYVAKYT®) for
the treatment of adults with ASM, SM-AHN or MCL, after at least one
systemic therapy, and adults with unresectable or metastatic GIST
harboring the PDGFRA D842V mutation. Please click here to see the
full U.S. Prescribing Information for AYVAKIT, and click here to
see the European Summary of Product Characteristics for
AYVAKYT.
AYVAKIT/AYVAKYT is not approved for the treatment of any other
indication in the U.S. or Europe.
The FDA granted breakthrough therapy designation to AYVAKIT for the
treatment of moderate to severe indolent SM.
To learn about ongoing or planned clinical trials, contact
Blueprint Medicines at medinfo@blueprintmedicines.com or
1-888-BLU-PRNT (1-888-258-7768). Additional information is
available at blueprintclinicaltrials.com or
clinicaltrials.gov.
About Systemic Mastocytosis
Systemic mastocytosis (SM) is a rare disease primarily driven by
the KIT D816V mutation. Uncontrolled proliferation and activation
of mast cells result in chronic, severe and often unpredictable
symptoms for patients across the spectrum of SM. The vast majority
of those affected have non-advanced (indolent or smoldering) SM,
with debilitating symptoms that lead to a profound, negative impact
on quality of life. A minority of patients have advanced SM, which
encompasses a group of high-risk SM subtypes including ASM, SM-AHN
and MCL. In addition to mast cell activation symptoms, advanced SM
is associated with organ damage due to mast cell infiltration and
poor survival. Across advanced SM subtypes, the median overall
survival is approximately 3.5 years in ASM, approximately two years
in SM-AHN and less than six months in MCL.
Debilitating symptoms, including anaphylaxis, maculopapular
rash, pruritis, diarrhea, brain fog, fatigue and bone pain, often
persist across all forms of SM despite treatment with a number of
symptom-directed therapies. Patients often live in fear of severe,
unexpected symptoms, have limited ability to work or perform daily
activities, and isolate themselves to protect against unpredictable
triggers. Historically, there had been no approved therapies for
the treatment of SM that selectively inhibit D816V mutant KIT.
About the PIONEER Trial
PIONEER is a randomized, double-blind, placebo-controlled,
registrational trial evaluating AYVAKIT in patients with
non-advanced SM. The trial includes three parts: dose-finding Part
1, registrational Part 2 and long-term treatment Part 3. Key trial
endpoints include the change in patient-reported disease symptoms
as measured by the ISM-SAF TSS, patient-reported quality of life,
quantitative measures of mast cell burden and safety. Patients who
completed Part 1 or 2 were eligible to participate in Part 3. All
patients receive AYVAKIT treatment during Part 3, including those
rolling over from the control arm. For more information about the
PIONEER trial, please visit www.clinicaltrials.gov
(ClinicalTrials.gov Identifier: NCT03731260).
About Blueprint Medicines
Blueprint Medicines is a global precision therapy company that
invents life-changing therapies for people with cancer and blood
disorders. Applying an approach that is both precise and agile, we
create medicines that selectively target genetic drivers, with the
goal of staying one step ahead across stages of disease. Since
2011, we have leveraged our research platform, including expertise
in molecular targeting and world-class drug design capabilities,
to rapidly and reproducibly translate science into a broad pipeline
of precision therapies. Today, we are delivering approved medicines
directly to patients in the United
States and Europe, and we
are globally advancing multiple programs for systemic mastocytosis,
lung cancer and other genomically defined cancers, and cancer
immunotherapy. For more information, visit
www.BlueprintMedicines.com and follow us on Twitter
(@BlueprintMeds) and LinkedIn.
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 to submit a supplemental new drug application
(sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT
in patients with non-advanced SM, with a subsequent submission of a
type II variation marketing authorization application to the
European Medicines Agency (EMA), plans and timing for presenting
detailed data from the PIONEER trial of AYVAKIT in patients with
non-advanced SM, and expectations regarding the potential benefits
of AYVAKIT in treating patients with non-advanced SM. The words
"aim," "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 impact of the
COVID-19 pandemic to Blueprint Medicines' business, operations,
strategy, goals and anticipated milestones, including Blueprint
Medicines' ongoing and planned research and discovery activities,
ability to conduct ongoing and planned clinical trials, clinical
supply of current or future drug candidates, commercial supply of
current or future approved products, and launching, marketing and
selling current or future approved products; Blueprint Medicines'
ability and plans in continuing to establish and expand a
commercial infrastructure, and successfully launching, marketing
and selling current or future approved products; Blueprint
Medicines' ability to successfully expand the approved indications
for AYVAKIT/AYVAKYT or obtain marketing approval for
AYVAKIT/AYVAKYT in additional geographies in the future; the delay
of any current or planned clinical trials or the development of
Blueprint Medicines' current or future drug candidates; Blueprint
Medicines' advancement of multiple early-stage efforts; Blueprint
Medicines' ability to successfully demonstrate the safety and
efficacy of its drug candidates and gain approval of its drug
candidates or of an approved product in an additional indication on
a timely basis, if at all; the preclinical and clinical results for
Blueprint Medicines' drug candidates, which may not support further
development of such drug candidates either as monotherapies or in
combination with other agents or may impact the anticipated timing
of data or regulatory submissions; the risk that "topline" data
from our clinical trials that we announce or publish from time to
time may change as more patient data become available and are
subject to confirmation, audit, and verification procedures that
could result in material changes in the final data; the timing of
the initiation of clinical trials and trial cohorts at clinical
trial sites and patient enrollment rates; actions of regulatory
agencies, which may affect the initiation, timing and progress of
clinical trials; Blueprint Medicines' ability to obtain, maintain
and enforce patent and other intellectual property protection for
AYVAKIT/AYVAKYT; Blueprint Medicines' ability to develop and
commercialize companion diagnostic tests for AYVAKIT/AYVAKYT;
Blueprint Medicines' ability to successfully expand its operations,
research platform and portfolio of therapeutic candidates, and the
timing and costs thereof; and the success of Blueprint Medicines'
current and future collaborations, financing arrangements,
partnerships or licensing arrangements. These and other risks and
uncertainties are described in greater detail in the section
entitled "Risk Factors" in Blueprint Medicines' filings with the
Securities and Exchange Commission (SEC), including Blueprint
Medicines' most recent Annual Report on Form 10-K, as supplemented
by its most recent Quarterly Report on Form 10-Q and any other
filings that Blueprint Medicines has made or 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. Except as required by law, Blueprint
Medicines explicitly disclaims any obligation to update any
forward-looking statements.
Trademarks
Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos
are trademarks of Blueprint Medicines Corporation.
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