-- AYVAKIT achieved a statistically
significant and clinically meaningful improvement in total symptom
score that deepened over time, with improvements shown across all
individual symptoms --
-- AYVAKIT achieved a statistically
significant and clinically meaningful improvement on the
Mastocytosis Quality of Life Questionnaire (MC-QoL) --
-- AYVAKIT had a favorable safety profile
compared to placebo, supporting potential for chronic treatment
--
-- Blueprint Medicines to host investor
webcast tomorrow, February 27, 2023,
at 8:00 a.m. ET --
CAMBRIDGE, Mass., Feb. 26,
2023 /PRNewswire/ -- Blueprint Medicines Corporation
(NASDAQ: BPMC) today announced detailed results from the PIONEER
trial of AYVAKIT® (avapritinib) in patients with
indolent systemic mastocytosis (SM). As previously reported,
AYVAKIT achieved statistically significant and clinically
meaningful improvements on the primary and all key secondary
endpoints. New results further highlight the benefits of AYVAKIT on
pathological mast cell burden, disease symptoms – including total
symptom score (TSS), most severe symptom and all individual
symptoms – and quality of life. Across clinical measures,
improvements continued to deepen over time in patients treated with
AYVAKIT through 48 weeks. AYVAKIT was well-tolerated with a safety
profile favorable to placebo, and 96 percent of patients in the
AYVAKIT arm opted to continue treatment in the open-label extension
study.
![Print Print](https://mma.prnewswire.com/media/221118/blueprint_medicines_logo.jpg)
Based on these data, Blueprint Medicines submitted a
supplemental new drug application (sNDA) for AYVAKIT to the U.S.
Food and Drug Administration (FDA) and a type II variation
marketing authorization application (MAA) for AYVAKYT®
to the European Medicines Agency (EMA) for the treatment of
patients with indolent SM. The FDA has granted priority review to
the sNDA for AYVAKIT with a Prescription Drug User Fee Act (PDUFA)
action date of May 22, 2023, and the
EMA has validated the MAA for AYVAKYT.
"Patients with indolent systemic mastocytosis may experience
debilitating symptoms, including skin lesions which can flare
often, daily abdominal pain and diarrhea, as well as bone pain,
brain fog and fatigue. These symptoms profoundly impact quality of
life, the ability to work and opportunities to spend time with
family," said Mariana Castells,
M.D., Ph.D., Director, Mastocytosis Center, Brigham and Women's
Hospital, and an investigator on the PIONEER trial. "AYVAKIT was
designed to target KIT D816V, the underlying cause of most cases of
indolent SM, with the potential to modify the disease biology
across multiple organ systems. AYVAKIT significantly reduced mast
cell burden and improved patients' symptoms and quality of life in
the PIONEER trial, representing the first positive registrational
study for the treatment of indolent SM. The magnitude and
consistency of benefit shown by AYVAKIT highlights its potential to
become a major therapeutic breakthrough."
"The detailed PIONEER results reported today mark the
culmination of a decade of research and collaboration with the
systemic mastocytosis community, with the goal of transforming
treatment for all patients living with SM," said Becker Hewes,
M.D., Chief Medical Officer at Blueprint Medicines. "AYVAKIT
has shown rapid, durable and clinically meaningful benefits across
trial endpoints, with improvements deepening over time, and a
well-tolerated safety profile. These compelling data underscore the
potential of AYVAKIT to transform the standard of care for a broad
range of patients. We are collaborating with regulatory authorities
to make this treatment available to people with indolent SM as
quickly as possible."
Data Highlights from the PIONEER Trial
In the randomized, double-blind, placebo-controlled part of the
PIONEER trial, 141 patients received AYVAKIT 25 mg once daily plus
best supportive care and 71 patients received placebo plus best
supportive care (placebo) at 49 sites in 13 countries. The study
included adults with an indolent SM diagnosis confirmed by central
pathology review, and moderate-to-severe symptom burden despite an
optimized regimen of best supportive care. All patients were able
to continue symptom-directed therapy throughout the trial and,
following completion of the 24-week treatment period, had the
option to receive AYVAKIT in an open-label extension study.
Baseline patient demographics were balanced between treatment arms
and reflected significant disease burden. Disease symptoms were
assessed using the Indolent SM Symptom Assessment Form
(ISM-SAF).
AYVAKIT achieved rapid, durable and statistically significant
reductions on all measures of pathological mast cell burden
compared to placebo at 24 weeks.
Outcome
measure
|
AYVAKIT
|
Placebo
|
p-value
|
Proportion with ≥50%
reduction in serum tryptase
|
53.9 %
|
0 %
|
p<0.0001
|
Proportion with ≥50%
reduction in KIT D816V variant allele fraction
|
67.8 %
|
6.3 %
|
p<0.0001
|
Proportion with ≥50%
reduction in bone marrow mast cell aggregates
|
52.8 %
|
22.8 %
|
p<0.0001
|
AYVAKIT achieved a statistically significant and clinically
meaningful improvement in TSS compared to placebo at 24 weeks, with
improvements observed across all symptoms measured by the ISM-SAF
that deepened over time.
Outcome
measure
|
AYVAKIT
|
Placebo
|
p-value
|
24 weeks
|
48 weeks
|
24 weeks
|
24 weeks
|
Mean change in
TSS
|
-15.6 points
|
-20.2 points
|
-9.2 points
|
p=0.003
|
Proportion with ≥30%
reduction in TSS
|
45.4 %
|
60.7 %
|
29.6 %
|
p=0.009
|
Proportion with ≥50%
reduction in TSS
|
24.8 %
|
39.3 %
|
9.9 %
|
p=0.005
|
- AYVAKIT achieved a statistically significant improvement in
mean change in most severe symptom score compared to placebo at 24
weeks (p=0.015).
AYVAKIT achieved a statistically significant and clinically
meaningful improvement in the mean percent change in Mastocytosis
Quality of Life Questionnaire (MC-QoL) total score compared to
placebo at 24 weeks.
Outcome
measure
|
AYVAKIT
|
Placebo
|
p-value
|
Mean percent change in
MC-QoL total score
|
-34.3 %
|
-17.9 %
|
p=0.001
|
AYVAKIT was well-tolerated with a favorable safety profile
compared to placebo, supporting the potential for long-term
treatment.
- Across treatment arms, most adverse events (AEs) were mild to
moderate in severity, and treatment-related AEs leading to
discontinuations were low for both arms (1.4% each).
- Serious AEs were reported more frequently in the placebo arm
(11.3%) compared to the AYVAKIT arm (5.0%).
- The most common treatment-related AEs (≥5 percent) were
headache (7.8% AYVAKIT vs. 9.9% placebo), nausea (6.4% AYVAKIT vs.
8.5% placebo), peripheral edema (6.4% AYVAKIT vs. 1.4% placebo),
periorbital edema (6.4% AYVAKIT vs. 2.8% placebo) and dizziness
(2.8% AYVAKIT vs. 7.0% placebo). Most edema AEs were Grade 1, and
none led to treatment discontinuation.
Copies of Blueprint Medicines data presentations from the
American Academy of Allergy, Asthma & Immunology (AAAAI) Annual
Meeting are available in the "Science—Publications and
Presentations" section of the company's website at
www.BlueprintMedicines.com.
Investor Conference Call Information
Blueprint Medicines will host a live conference call and
webcast at 8:00 a.m. ET (7:00 a.m.
CT) tomorrow, February
27, 2023 to discuss the PIONEER trial data of AYVAKIT
in indolent SM. The conference call may be accessed by dialing
844-200-6205 (domestic) or 929-526-1599 (international), and
referring to conference ID 163491. 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.
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 driven by the KIT
D816V mutation in about 95 percent of cases. Uncontrolled
proliferation and activation of mast cells result in chronic,
severe and often unpredictable symptoms across multiple organ
systems. Most of those affected have non-advanced (indolent or
smoldering) SM, and among these patients, the vast majority have
indolent SM. A broad range of symptoms, including anaphylaxis,
maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone
pain, frequently persist in patients with non-advanced SM despite
treatment with multiple symptom-directed therapies. This burden of
disease can lead to a profound, negative impact on quality of life.
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. Currently,
there are no approved therapies for the treatment of non-advanced
SM.
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.
About the PIONEER Trial
PIONEER is a randomized, double-blind, placebo-controlled,
registrational trial evaluating AYVAKIT in patients with indolent
SM. The trial includes three parts: dose-finding Part 1,
registrational Part 2 and open-label extension Part 3. Key trial
endpoints include the change in patient-reported disease symptoms
as assessed by the ISM-SAF TSS, patient-reported quality of life,
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 placebo 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 our
approved medicines to patients in the United
States and Europe, and we are globally advancing multiple
programs for systemic mastocytosis, lung cancer, breast 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 the FDA's approval of an sNDA for AYVAKIT for
the treatment of indolent SM; expectations regarding the potential
benefits of AYVAKIT in treating patients with indolent SM;
statements regarding plans, timelines and expectations for
interactions with the FDA, EMA and other regulatory authorities;
statements regarding plans and expectations for Blueprint
Medicines' current or future approved drugs and drug candidates;
the potential benefits of any of Blueprint Medicines' current or
future approved drugs or drug candidates in treating patients; and
Blueprint Medicines' financial performance, strategy, goals and
anticipated milestones, business plans and focus. 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: the risk that the partial clinical hold on the VELA
trial may or may not be resolved in a timely manner; there may be
additional adverse events observed that could impact the extent of
the partial clinical hold or Blueprint Medicines' resolution of the
partial clinical hold; there may be amendments to the trial
protocol that impact the timing of the trial or evaluation of the
data; preliminary activity and safety data may not be
representative of more mature data; the COVID-19 pandemic may
impact Blueprint Medicines' business, operations, strategy, goals
and anticipated milestones, including ongoing and planned research
and discovery activities, Blueprint Medicines' ability to conduct
ongoing and planned clinical trials; the risk of delay of any
current or planned clinical trials or the development of Blueprint
Medicines' current or future drug candidates; risks related to
Blueprint Medicines' ability to successfully demonstrate the safety
and efficacy of its drug candidates and gain approval of its drug
candidates on a timely basis, if at all; preclinical and clinical
results for Blueprint Medicines' drug candidates 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 timing of the
initiation of clinical trials and trial cohorts at clinical trial
sites and patient enrollment rates may be delayed or slower than
anticipated; actions of regulatory agencies may affect the
initiation, timing and progress of clinical trials; risks related
to Blueprint Medicines' ability to obtain, maintain and enforce
patent and other intellectual property protection for its products
and current or future drug candidates it is developing; and the
success of Blueprint Medicines' current and future collaborations,
financing arrangements, partnerships or licensing arrangements. 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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