-- Updated data show AYVAKIT® (avapritinib)
was safe and effective for long-term treatment of ISM, with
sustained symptom and quality-of-life benefit and no new safety
signals with multiple years of therapy --
-- AYVAKIT-treated patients achieved
improvements in bone health based on an analysis of bone mineral
density scans, underscoring the importance of treating patients
early in the ISM disease course --
-- BLU-808 healthy volunteer trial results
demonstrate wide therapeutic window for modulating mast cell
activity, affirming potential as best- and first-in-class oral
wild-type KIT inhibitor --
CAMBRIDGE, Mass., Feb. 28,
2025 /PRNewswire/ -- Blueprint Medicines Corporation
(Nasdaq: BPMC) today announced data presentations reflecting its
ongoing efforts to innovate the treatment of mast cell-driven
diseases. The presentations include three-year median follow-up
data from the registrational PIONEER trial demonstrating the strong
long-term efficacy and safety of AYVAKIT® (avapritinib) in patients
with indolent systemic mastocytosis (ISM), and real-world evidence
further characterizing the substantial burden of the disease,
highlighting the urgency to treat. In addition, the company will
report positive data from the Phase 1 healthy volunteer trial
evaluating BLU-808, an investigational, highly potent and selective
oral inhibitor of wild-type KIT, consistent with top-line data
previously announced in January 2025.
A total of 14 data presentations, including two oral presentations,
will be reported at the 2025 American Academy of Allergy, Asthma
& Immunology (AAAAI) / World Allergy Organization (WAO) Joint
Congress being held February 28-March
3 in San Diego.
"We are incredibly proud to showcase our mast cell therapy
portfolio at AAAAI / WAO, with 14 presentations highlighting more
than a decade of leadership and collaboration with the mast cell
disease community, including renowned medical institutions
pioneering innovative research and multi-disciplinary patient
care," said Becker Hewes, M.D., Chief Medical Officer at Blueprint
Medicines. "In ISM, new data have reinforced that AYVAKIT was very
well-tolerated after multiple years of treatment, with a low
discontinuation rate and safety results that have remained
consistent with the safety profile from the placebo-controlled
study as summarized in the FDA-approval label. This updated AYVAKIT
data is particularly important for clinicians considering long-term
treatment options for their ISM patients. Further, we are
building on our foundational expertise in ISM with our oral
wild-type KIT inhibitor BLU-808, with healthy volunteer data
showing a differentiated clinical profile and wide therapeutic
index that supports broad development across a range of mast cell
diseases. Based on these data, we are initiating multiple
proof-of-concept trials, with initial data expected later this
year."
AYVAKIT: PIONEER Three-Year Efficacy and Safety Data in
ISM
- AYVAKIT 25 mg once daily (QD) was well-tolerated and no new
safety signals were identified with a median of 3 years of
exposure, with some patients out to five years of treatment. The
most common treatment-related adverse events (AEs; ≥5 percent) were
low-grade peripheral edema, periorbital edema, headache and
nausea.
- AYVAKIT 25 mg QD led to robust and durable improvements in
overall symptoms, individual symptom domains (skin,
gastrointestinal, neurocognitive) and quality of life through 144
weeks of treatment.
- In patients who had high disease burden and escalated to
AYVAKIT 50 mg QD (median follow-up: 10.6 months since escalation),
treatment was well-tolerated, with side effects consistent with
those reported at AYVAKIT 25 mg QD and no patients discontinuing
due to AEs. Nearly all patients (93 percent) had improved or stable
benefits in overall symptoms.
Low Bone Density: Positive Clinical Impact of AYVAKIT and
Real-World Prevalence in ISM
- In a single-site case series from the PIONEER trial, AYVAKIT
showed clinically meaningful and durable improvements in bone
density, including in the lumbar spine, femoral neck and total
proximal femur.
- In real-world data generated from Mayo Clinic electronic health
records, 67 percent of ISM patients had osteoporosis/osteopenia
compared to 34 percent in a matched control cohort
(p<0.0001).
AYVAKIT: Clinical Benefits in Patients with Undetected KIT
D816V by ddPCR Assay
- In the PIONEER trial, 15 percent of patients with ISM did not
have KIT D816V mutations detected by the commercially available
Droplet Digital Polymerase Chain Reaction (ddPCR) assay. Within
this group, most patients had KIT mutations identified by the more
sensitive duplex sequencing method, and these patients achieved
similar reductions in serum tryptase and improvements in symptoms
as those with detectable KIT mutations by the ddPCR assay.
BLU-808: Positive Healthy Volunteer Data
- In the Phase 1 single-ascending dose (SAD) and
multiple-ascending dose (MAD, 14-day dosing) trial, BLU-808 was
well-tolerated at all doses tested. There were no serious AEs, no
discontinuations or dose modifications due to AEs, and no
significant changes in laboratory measures.
- BLU-808 achieved dose-dependent serum tryptase reductions
exceeding 80 percent, reflecting evidence of mast cell target
engagement.
- BLU-808 had a half-life supporting once-daily oral dosing and
showed sustained target coverage across a range of doses.
Blueprint Medicines' AAAAI / WAO data presentations are listed
below. Copies of the data presentations will be available in the
"Science—Publications and Presentations" section of the company's
website at www.BlueprintMedicines.com.
- Oral Presentation: Assessing Real-World Natural History of
Indolent Systemic Mastocytosis: Retrospective Matched Cohort Study
from Mayo Clinic Electronic Health Records (Abstract 955 –
Monday, March 3)
- Oral Presentation: Responses to Avapritinib in Patients without
Detectable KIT Mutations by ddPCR in Peripheral Blood Highlight
Diagnostic Challenges and Opportunities in Indolent Systemic
Mastocytosis (Abstract 965 – Monday,
March 3)
- Poster Presentation: Patient Reported Burden of Indolent
Systemic Mastocytosis in White vs. Non-White Patients (Abstract
220 – Friday, February 28)
- Poster Presentation: Identification of Clonal Mast Cell Disease
in Patients with Anaphylaxis or Evidence of Systemic Mast Cell
Activation: A Post Hoc Analysis from PROSPECTOR (Abstract 301 –
Saturday, March 1)
- Poster Presentation: Avapritinib Impacts the Plasma
Inflammatory Proteome in Patients with Indolent Systemic
Mastocytosis (Abstract 517 – Saturday,
March 1)
- Poster Presentation: Multiple Proteins Correlate with Tryptase
Levels in Patients with Indolent Systemic Mastocytosis (ISM):
Preliminary Results of Plasma Proteomic Analysis in PIONEER
(Abstract 518 – Saturday, March
1)
- Poster Presentation: Comprehensive Analysis of Immunoglobulin E
Levels in Healthy Donors and Patients with Indolent Systemic
Mastocytosis Enrolled on the PIONEER Trial of Avapritinib
(Abstract 521 – Saturday, March
1)
- Poster Presentation: Avapritinib and Bone Health in Indolent
Systemic Mastocytosis: Learnings from the PIONEER Trial
(Abstract 527– Saturday, March
1)
- Poster Presentation: PREDICT-SM: Development of Machine
Learning Models to Support Screening for Undiagnosed Systemic
Mastocytosis (Abstract 530 – Saturday,
March 1)
- Poster Presentation (Trial in Progress): HARBOR: An Ongoing
Phase 2/3 Study of Elenestinib in Patients with Indolent Systemic
Mastocytosis (Abstract 533 – Saturday,
March 1)
- Poster Presentation: Long-Term Quality of Life and Safety in
Patients with Indolent Systemic Mastocytosis Treated with
Avapritinib in the PIONEER Study (Abstract 534 – Saturday, March 1)
- Poster Presentation: BLU-808: A Potent and Selective Oral Small
Molecule Wild-Type KIT Tyrosine Kinase Inhibitor for Allergic
Conditions (Abstract 535 – Saturday,
March 1)
- Poster Presentation: Utility of Large Language Models to
Quantify Diagnostic Delays in Systemic Mastocytosis: A Multi-Center
Real World Study (Abstract 544 – Saturday, March 1)
- Poster Presentation: Safety and Pharmacokinetics (PK) of
BLU-808 Following Oral Dosing in Healthy Volunteers (Abstract
698 – Sunday, March 2)
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.
Until 2023, there were 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 aggressive SM (ASM), SM
with an associated hematological neoplasm (SM-AHN) and mast cell
leukemia (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 ASM, SM-AHN and
MCL, and adults with unresectable or metastatic gastrointestinal
stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including
PDGFRA D842V mutations. Under the brand name AYVAKYT®
(avapritinib), this medicine is approved by the European
Commission for the treatment of adults with ISM with moderate
to severe symptoms inadequately controlled on symptomatic
treatment, adults with ASM, SM-AHN and MCL, after at least one
systemic therapy, and adults with unresectable or metastatic GIST
harboring the PDGFRA D842V mutation. The therapy is not recommended
for the treatment of patients with low platelet counts (less than
50,000/µL).
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.
Important Safety Information
Cognitive Effects — Cognitive adverse reactions can
occur in patients receiving AYVAKIT and occurred in 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, withhold AYVAKIT and then
resume at the same dose, or permanently discontinue AYVAKIT.
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 contraception during treatment with
AYVAKIT and for 6 weeks after the final dose. Advise women not to
breastfeed during treatment with AYVAKIT and for 2 weeks following
the final dose.
Adverse Reactions — 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 or inducers. If
contraception requires estrogen, limit ethinyl estradiol to ≤20 mcg
unless a higher dose is necessary.
To report suspected adverse reactions, contact Blueprint
Medicines Corporation at 1-888-258-7768 or the FDA at
1-800-FDA-1088 or visit www.fda.gov/medwatch.
AYVAKIT is available in 25-mg, 50-mg, 100-mg and 200-mg
tablets.
Please click here to see the full Prescribing
Information for AYVAKIT.
About Blueprint Medicines
Blueprint Medicines is a global, fully integrated
biopharmaceutical company that invents life-changing medicines. We
seek to alleviate human suffering by solving important medical
problems in two core focus areas: allergy/inflammation and
oncology/hematology. Our approach begins by targeting the root
causes of disease, using deep scientific knowledge in our core
focus areas and drug discovery expertise across multiple
therapeutic modalities. We have a track record of success with two
approved medicines, including AYVAKIT®/AYVAKYT® (avapritinib) which
we are bringing to patients with systemic mastocytosis (SM) in
the U.S. and Europe. Leveraging our established
research, development, and commercial capability and
infrastructure, we now aim to significantly scale our impact by
advancing a broad pipeline of programs ranging from early science
to advanced clinical trials in mast cell diseases including SM and
chronic urticaria, breast cancer and other solid tumors. 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 and
potential benefits of 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 to 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 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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