-- First and only treatment approved by FDA
for indolent SM --
CAMBRIDGE, Mass., May 23,
2023 /PRNewswire/ -- Blueprint Medicines
Corporation (Nasdaq: BPMC) today announced that NEJM
Evidence, a journal from The New England Journal of Medicine
Group, has published detailed results from the PIONEER trial of
AYVAKIT® (avapritinib) in patients with indolent systemic
mastocytosis (ISM). Data reported in the publication show that
AYVAKIT achieved statistically significant and clinically
meaningful benefits across efficacy measures including disease
symptoms and pathological mast cell burden, which continued to
improve over time through 48 weeks. In addition, AYVAKIT
demonstrated a favorable safety profile relative to placebo.
On May 22, 2023, AYVAKIT became
the first and only medicine approved by the U.S. Food and Drug
Administration (FDA) for the treatment of adults with ISM. AYVAKIT
was designed to potently and selectively inhibit KIT D816V, the
primary underlying driver of the disease. ISM represents the vast
majority of cases of systemic mastocytosis (SM), a rare hematologic
disorder that can lead to debilitating symptoms across multiple
organ symptoms and a profound impact on patients' quality of
life.
"Patients with indolent systemic mastocytosis can experience a
range of severe, life-altering symptoms and emotional hardships.
The disorder can significantly affect patients' ability to serve as
active members of their families, workplaces and broader
communities, and may lead individuals to 'live in a bubble' at home
in an attempt to avoid unpredictable triggers," said Mariana Castells, M.D., Ph.D., Director,
Mastocytosis Center, Brigham and Women's Hospital and co-first
author of the paper. "Since I began specializing in mast cell
disorders several decades ago, I have been waiting for a treatment
that targeted the primary root cause of indolent systemic
mastocytosis and enabled broad clinical benefits for patients with
uncontrolled disease despite significant polypharmacy use. The
impact of AYVAKIT across trial endpoints – from mast cell burden to
symptoms and quality of life – offers the opportunity to redefine
the standard of care in indolent systemic mastocytosis and brings a
renewed sense of hope for all those living with the disorder."
"This publication features the largest dataset ever reported in
indolent systemic mastocytosis and the first positive
registrational study for this disease, representing a landmark
achievement in our long-term collaboration with clinical experts
and the systemic mastocytosis community to advance patient care,"
said Becker Hewes, M.D., Chief Medical Officer at Blueprint
Medicines. "Our deep commitment, knowledge and understanding of
systemic mastocytosis has enabled us to develop a transformative
targeted treatment that can significantly improve outcomes for
patients. Blueprint Medicines has been pioneering research and
development in the field of systemic mastocytosis for over a
decade, and following the approval of AYVAKIT in indolent systemic
mastocytosis, we are focused on delivering this major therapeutic
advancement to a broad range of patients with the disease."
Highlights from the NEJM Evidence Publication
PIONEER is a randomized, double-blind, placebo-controlled trial
in which 141 patients received AYVAKIT 25 mg once daily plus best
supportive care (AYVAKIT) and 71 patients received placebo plus
best supportive care (placebo). Disease symptoms were assessed
using the ISM Symptom Assessment Form (ISM-SAF). As previously
reported, AYVAKIT met the primary and all key secondary endpoints,
which were evaluated from baseline to 24 weeks, and showed
deepening clinical efficacy through 48 weeks of treatment. Overall,
96 percent of patients with AYVAKIT completed 24 weeks of treatment
and opted to cross over to the open-label extension study.
Key published results include:
- Patients treated with AYVAKIT achieved rapid, durable and
statistically significant reductions on all measures of
pathological mast cell burden, including serum tryptase, KIT D816V
variant allele fraction and bone marrow mast cells.
- AYVAKIT achieved statistically significant and clinically
meaningful benefits in overall symptoms – as measured by the
ISM-SAF Total Symptom Score (TSS) – compared to placebo at 24
weeks, with improvements deepening through 48 weeks. In addition,
AYVAKIT showed improvements over placebo on the most severe symptom
and across all individual symptoms measured.
- AYVAKIT showed clinically meaningful improvements in multiple
exploratory endpoints of quality of life, including a
disease-specific measure – Mastocytosis Quality of Life
Questionnaire (MC-QoL) – and general health status measures such as
European Quality of Life Visual Analogue Scale (EQ-VAS), Patient
Global Impression of Severity (PGIS) and 12-Item Short-Form Health
Survey (SF-12).
- AYVAKIT showed a favorable safety profile, with most adverse
events (AEs) mild to moderate in severity. The serious AE rate was
5.0 percent for AYVAKIT and 11.3 percent for placebo. The most
common treatment-emergent AEs for AYVAKIT (incidence ≥5 percent and
at least twice the rate of placebo) were flushing, edema, increased
blood alkaline phosphatase and insomnia.
The paper, titled "Avapritinib versus Placebo in Indolent
Systemic Mastocytosis," was published in NEJM Evidence on
May 23, 2023 and can be found here:
https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200339.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is a precision therapy approved by the FDA
for the treatment of three indications: adults with ISM, 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. The vast majority of those affected have indolent systemic
mastocytosis (ISM). A broad range of symptoms, including
anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog,
fatigue and bone pain, frequently persist in patients with ISM
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.
Historically, there had been no approved therapies for the
treatment of ISM.
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.
Important Safety Information
Intracranial Hemorrhage—Serious intracranial hemorrhage (ICH)
may occur with AYVAKIT treatment; fatal events occurred in <1%
of patients. Overall, ICH (eg, subdural hematoma, ICH, and cerebral
hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT
in clinical trials. In Advanced SM patients who received AYVAKIT at
200 mg daily, ICH occurred in 2 of 75 patients
(2.7%) who had platelet counts ≥50 x 109/L
prior to initiation of therapy and in
3 of 80 patients (3.8%) regardless of platelet
counts. In ISM patients, no events of ICH occurred in the
246 patients who received any dose of AYVAKIT in the PIONEER
study.
Monitor patients closely for risk factors of ICH which may
include history of vascular aneurysm, ICH or cerebrovascular
accident within the prior year, concomitant use of anticoagulant
drugs, or thrombocytopenia.
Symptoms of ICH may include headache, nausea, vomiting, vision
changes, or altered mental status. Advise patients to seek
immediate medical attention for signs or symptoms of ICH.
Permanently discontinue AYVAKIT if ICH of any grade occurs. In
Advanced SM patients, a platelet count must be performed prior to
initiating therapy. AYVAKIT is not recommended in Advanced SM
patients with platelet counts <50 x 109/L.
Following treatment initiation, platelet counts must be performed
every 2 weeks for the first 8 weeks. After 8 weeks of treatment,
monitor platelet counts every 2 weeks or as clinically indicated
based on platelet counts. Manage platelet counts of <50 x
109/L by treatment interruption or dose reduction.
Cognitive Effects—Cognitive adverse reactions can occur in
patients receiving AYVAKIT and occurred in 33% of 995 patients
overall in patients who received AYVAKIT in clinical trials
including: 28% of 148 Advanced SM patients (3% were
Grade ≥3), and 7.8% of patients with ISM who received
AYVAKIT + best supportive care (BSC) versus 7.0% of
patients who received placebo + BSC (<1% were
Grade 3). Depending on the severity and indication, withhold
AYVAKIT and then resume at same dose or at a reduced dose upon
improvement, or permanently discontinue.
Photosensitivity—AYVAKIT may cause photosensitivity reactions.
In all patients treated with AYVAKIT in clinical trials (n=1049),
photosensitivity reactions occurred in 2.5% of patients.
Advise patients to limit direct ultraviolet exposure during
treatment with AYVAKIT and for one week after discontinuation of
treatment.
Embryo-Fetal Toxicity—AYVAKIT can cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females and males of reproductive
potential to use an effective method of contraception during
treatment with AYVAKIT and for 6 weeks after the final dose of
AYVAKIT. Advise women not to breastfeed during treatment with
AYVAKIT and for 2 weeks after the final dose.
Adverse Reactions—The most common adverse reactions (≥20%)
in patients with Advanced SM were edema, diarrhea, nausea, and
fatigue/asthenia.
The most common adverse reactions (≥10%) in patients with
ISM were eye edema, dizziness, peripheral edema, and flushing.
Drug Interactions—Avoid coadministration of AYVAKIT with strong
or moderate CYP3A inhibitors. If coadministration with a moderate
CYP3A inhibitor cannot be avoided in patients with Advanced SM,
reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with
strong or moderate CYP3A inducers.
To report suspected adverse reactions, contact Blueprint
Medicines Corporation at 1-888-258-7768 or FDA at
1-800-FDA-1088 or http://www.fda.gov/medwatch.
Please click here to see the full Prescribing
Information for AYVAKIT.
About the PIONEER Trial
PIONEER is a randomized, double-blind, placebo-controlled,
registrational trial evaluating AYVAKIT in patients with ISM. 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 Blueprint Medicines' views with respect to the
implications of the FDA approval of AYVAKIT/AYVAKYT for SM
patients; the potential benefits of Blueprint Medicines' current
and future approved drugs or drug candidates in treating patients,
including expectations regarding the potential of AYVAKIT/AYVAKYT
to address SM subtypes; and Blueprint Medicines' 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, risks and uncertainties related to our ability and
plans in continuing to expand Blueprint Medicines' 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 our 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 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; 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 its products or any drug
candidates it is developing; Blueprint Medicines' ability to
develop and commercialize companion diagnostic tests for its
products or any of its current and future drug candidates;
Blueprint Medicines' ability to successfully expand its research
platform and the costs thereof; and the success of Blueprint
Medicines' current and future collaborations, 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 its Annual Report on Form 10-K for the
year ended December 31, 2022, as
filed with the SEC on February 16,
2023, 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 assumes no
obligation to update or revise these forward-looking statements for
any reason, even if new information becomes available in the
future.
Trademarks
Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are
trademarks of Blueprint Medicines Corporation.
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SOURCE Blueprint Medicines Corporation