-- AYVAKIT data in patients with indolent
systemic mastocytosis show durable efficacy and favorable safety
supporting long-term treatment, consistent with real-world
experience observed in commercial setting --
-- Preclinical data for BLU-808, a highly
selective and potent oral wild-type KIT inhibitor with
best-in-class potential, supports development in chronic urticaria
and other mast cell diseases; on track to submit IND to FDA in Q2
2024 --
-- Breadth of data across 9 presentations,
including 2 oral, highlight scientific and clinical leadership
--
CAMBRIDGE, Mass., Feb. 23,
2024 /PRNewswire/ -- Blueprint Medicines Corporation
(Nasdaq: BPMC) today announced PIONEER trial results highlighting
the long-term efficacy and safety of AYVAKIT® (avapritinib) in
patients with indolent systemic mastocytosis (ISM), as well as
foundational preclinical data for BLU-808, an investigational
highly selective and potent oral inhibitor of wild-type KIT.
Blueprint Medicines will report a total of nine data presentations,
including two oral presentations, reflecting the company's
long-standing commitment to transform care for patients living with
mast cell disorders. The datasets are being reported at the 2024
American Academy of Allergy, Asthma & Immunology (AAAAI) Annual
Meeting being held February 23-26 in
Washington, D.C.
"PIONEER data show that long-term treatment with AYVAKIT led to
robust and durable clinical efficacy across a wide range of
symptoms, and a well-tolerated safety profile that has remained
remarkably consistent over time," said Becker Hewes, M.D., Chief
Medical Officer at Blueprint Medicines. "These compelling long-term
data, combined with the real-world experience of more than a
thousand patients currently on therapy in the U.S., indicate our
continued momentum in establishing AYVAKIT as a new standard of
care for patients living with ISM. With an SM franchise anchored by
AYVAKIT, and the opportunity to expand and extend our reach with
elenestinib, Blueprint Medicines is transforming treatment across
the spectrum of the disease and redefining what well-controlled
means for patients."
AYVAKIT: Durable Symptom Impact and Well-Tolerated Safety
Profile in Patients with ISM
Long-term data from the PIONEER trial show that AYVAKIT led to
robust improvements across all symptom domains (skin,
gastrointestinal, neurocognitive) at 24 weeks, with sustained
benefits through 48 weeks. In addition, patients treated with
placebo during the blinded portion of the trial had rapid and
durable symptom improvements upon cross-over to AYVAKIT. Symptom
improvements were assessed by the validated Indolent Systemic
Mastocytosis Symptom Assessment Form (ISM-SAF). After 48 weeks of
treatment with AYVAKIT, 35 percent of patients reduced or
discontinued use of best supportive care medicines. As of the
updated data cut, the last patient treated with AYVAKIT in the
blinded portion of the trial reached the 48-week timepoint.
With a median patient follow-up of 18 months, the safety profile
of AYVAKIT was consistent with previously reported results from the
6-month placebo-controlled portion of the trial, with no new safety
signals observed. Most adverse events (AEs) were mild or moderate
(Grade 1-2), and the most common treatment-related AEs (≥5 percent)
were peripheral edema, headache, periorbital edema and nausea. The
rate of treatment-related AEs leading to discontinuation remained
low (3 percent).
BLU-808: An Investigational, Potent and
Selective Wild-type KIT Inhibitor for Chronic Urticaria
and Other Mast Cell Diseases
Mast cells play a critical frontline role in a healthy immune
response; activation through KIT and other receptors leads to
degranulation and release of downstream effectors that mediate
inflammation. However, when mast cells are dysregulated, they are
drivers of multiple common allergic and inflammatory diseases such
as chronic urticaria, for which wild-type KIT is a clinically
validated therapeutic target. BLU-808 is an investigational, highly
selective and potent oral wild-type KIT inhibitor designed to
enable tolerability and flexibility to tailor treatment based on
disease severity and patient needs.
"The development of BLU-808 is another example of our proven
track record of designing exquisitely selective molecules that
inhibit important biologic targets. Specifically, our scientists
engineered BLU-808 to potently target wild-type KIT, while
maintaining a wide therapeutic index conducive to chronic
treatment," said Percy Carter,
Ph.D., Chief Scientific Officer at Blueprint Medicines. "The
BLU-808 program highlights our focused efforts to scale our science
in allergy/inflammation, leveraging our expertise in mast cell
biology and fully integrated R&D and commercial capabilities.
By targeting the root cause of a variety of inflammatory diseases,
BLU-808 represents a potential best-in-class mast cell modulator
that may benefit large patient populations with high medical
needs."
In foundational preclinical data reported at AAAAI, BLU-808
demonstrated a best-in-class selectivity and potency profile in
vitro. In multiple in vivo studies, BLU-808 treatment
led to dose-dependent inhibition and depletion of mast cells. In
addition, BLU-808 improved lung function in an ovalbumin-induced
asthma model. Based on these data, Blueprint Medicines expects to
submit an investigational new drug application for BLU-808 in the
second quarter of 2024, and subsequently plans to initiate a Phase
1 study in healthy volunteers. The initial development focus for
BLU-808 will be in chronic urticaria.
Blueprint Medicines' AAAAI data presentations are listed below.
Copies of the data presentations are available in the
"Science—Publications and Presentations" section of the company's
website at www.BlueprintMedicines.com.
Data Presentations
Presentation Title: BLU-808, a Potent and Selective
Small Molecule Inhibitor of Wild-type c-KIT for Mast Cell
Disorders
Session Title: Novel Treatment Approaches in Allergic
Disease, Poster Session
Session Date & Time: Friday,
February 23 from 3:15 – 4:15 p.m.
ET
Abstract Number: 189
Location: Convention Center, Level 2, Hall D
Presentation Title: Patient-Reported Outcome Measures in
Systemic Mastocytosis: A Systematic Review
Session Title: Mast Cell Disorders, Poster Session
Session Date & Time: Sunday,
February 25 from 9:45 – 10:45 a.m.
ET
Abstract Number: 689
Location: Convention Center, Level 2, Hall D
Presentation Title: Reductions in Polypharmacy for
Patients with Indolent Systemic Mastocytosis on Avapritinib
Session Title: Mast Cell Disorders, Poster Session
Session Date & Time: Sunday,
February 25 from 9:45 – 10:45 a.m.
ET
Abstract Number: 696
Location: Convention Center, Level 2, Hall D
Presentation Title: Systemic Mastocytosis: Shedding
Light on a Rare and Complicated Disease
Session Title: Mast Cell Disorders, Poster Session
Session Date & Time: Sunday,
February 25 from 9:45 – 10:45 a.m.
ET
Abstract Number: 691
Location: Convention Center, Level 2, Hall D
Presentation Title: The Five Dimensions of the ISM
Patient Experience – Uncovering the "Real-world" Experience of
Patients with Indolent Systemic Mastocytosis
Session Title: Mast Cell Disorders, Poster Session
Session Date & Time: Sunday,
February 25 from 9:45 – 10:45 a.m.
ET
Abstract Number: 693
Location: Convention Center, Level 2, Hall D
Presentation Title: Quantifying Diagnostic Delays in
Patients with Indolent and Aggressive Systemic Mastocytosis
Session Title: Mast Cell Disorders, Poster Session
Session Date & Time: Sunday,
February 25 from 9:45 – 10:45 a.m.
ET
Abstract Number: 692
Location: Convention Center, Level 2, Hall D
Oral Presentation Title: Exploring the Spectrum of
Indolent Systemic Mastocytosis: Analysis of High-Risk Disease
Features in the PIONEER Study
Session Title: Mast Cell Disorders: Bench to Bedside, Oral
Abstract Session
Session Date & Time: Sunday,
February 25 from 2:15 – 2:25 p.m.
ET
Abstract Number: 737
Location: Convention Center, Level 1, Room 144B
Oral Presentation Title: Prevalence of The KIT D816V
Mutation In Peripheral Blood (PB) of Patients With Evidence of
Systemic Mast Cell Activation (MCA): Results of The Prospective,
Multi-centered, Global PROSPECTOR Clinical Trial
Session Title: Mast Cell Disorders: Bench to Bedside, Oral
Abstract Session
Session Date & Time: Sunday,
February 25 from 2:25 – 2:35 p.m.
ET
Abstract Number: 739
Location: Convention Center, Level 1, Room 144B
Presentation Title: Avapritinib Decreased Symptom
Burden in Patients with Indolent Systemic Mastocytosis in the
Registrational Double-Blind, Placebo-Controlled PIONEER Study
Session Title: Novel Cellular and Molecular Pathways of
Allergic Inflammation, Featured Poster Session
Session Date & Time: Sunday,
February 25 from 4:45 – 6:15 p.m.
ET
Abstract Number: 783
Location: Convention Center, Level 3, Ballroom South
Prefunction
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.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is approved by the U.S. Food and Drug
Administration (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 by the European
Commission (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.
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.
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 Blueprint Medicines
Blueprint Medicines is a fully integrated, commercial-stage,
global biopharmaceutical company that invents life-changing
medicines in two core, strategic areas of allergy/inflammation and
oncology/hematology. We pursue discovery, development, and
commercialization of therapies that potently and selectively target
known drivers of disease, with focused investment in therapeutic
areas where we can leverage our core expertise and business
infrastructure to bring scale to our science. We are bringing
AYVAKIT®/AYVAKYT® (avapritinib) to people living with systemic
mastocytosis (SM) in the U.S. and Europe. Additionally, we have a pipeline of
research and development programs that range from early science to
advanced clinical trials in mast cell-mediated diseases, including
SM and chronic urticaria, breast cancer, and other solid tumors
vulnerable to CDK2 inhibition. For more information,
visit www.BlueprintMedicines.com and follow us
on X (formerly 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 expectations for the potential benefits of AYVAKIT in
treating patients with ISM; Blueprint Medicines' ability to
transform treatment across the spectrum of SM; the development of
BLU-808 and whether it has best-in-class potential; plans and
timing for submitting an IND to the FDA for BLU-808; 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' strategy, goals, 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 Blueprint Medicines'
ability and plans in continuing to build out 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 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
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 or any drug candidates it is
developing; 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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