-- New analyses showing AYVAKIT® (avapritinib)
significantly improved overall survival in advanced SM, when
indirectly compared to real-world data for prior standard
therapies, to be presented at EHA 2022 Congress --
-- Primary endpoint of PIONEER trial of
AYVAKIT in non-advanced SM to be updated to mean change in total
symptom score, previously a key secondary endpoint, based on U.S.
FDA recommendation --
-- On track to report top-line
registrational data from PIONEER trial in late summer 2022
--
-- Kate
Haviland, Chief Executive Officer, to present at Jefferies
Healthcare Conference today at 1:30 p.m.
EDT --
CAMBRIDGE, Mass., June 9, 2022
/PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC)
today announced updates on the AYVAKIT®/AYVAKYT® (avapritinib)
development program in systemic mastocytosis (SM):
- New analyses, which will be presented this week at the European
Hematology Association (EHA) 2022 Congress, add to the growing body
of clinical evidence supporting AYVAKIT as the standard of care for
patients with advanced SM. Findings showed AYVAKIT improved overall
survival (OS), as well as other clinical outcomes, in patients with
advanced SM, when indirectly compared to real-world data for prior
best available therapies. Based on these analyses, patients treated
with AYVAKIT had a 41 percent reduction in the risk of death
compared to patients treated with midostaurin and a 68 percent
reduction in the risk of death compared to patients treated with
cladribine. In total, Blueprint Medicines is supporting the
presentation of seven abstracts at the EHA 2022 Congress,
highlighting the company's leadership in SM.
- In addition, Blueprint Medicines plans to update the primary
endpoint of the registrational PIONEER trial of AYVAKIT in patients
with non-advanced SM, based on a written recommendation from the
U.S. Food and Drug Administration (FDA) on statistical
considerations ahead of the planned database lock. The mean
absolute change in total symptom score (TSS), previously a key
secondary endpoint, will be the primary endpoint and the proportion
of patients with a 30 percent or greater decrease in TSS,
previously the primary endpoint, will be a key secondary endpoint.
Both analyses were previously defined as key endpoints that the
PIONEER trial was powered to assess. In addition, both endpoints
are based on the Indolent SM Symptom Assessment Form, a
patient-reported outcomes tool that has been developed and
validated in collaboration with the SM community and global
regulatory authorities. Blueprint Medicines continues to plan to
report top-line data from the PIONEER trial in late summer 2022 and
submit a supplemental new drug application to the FDA for AYVAKIT
for non-advanced SM by the end of 2022.
"Based on the recommendation of the FDA, we have re-ordered
pre-planned efficacy analyses in Part 2 of the PIONEER trial,
elevating mean change in total symptom score, which characterizes
clinical benefit across all patients," said Becker Hewes, M.D.,
Chief Medical Officer of Blueprint Medicines. "Consistent with Part
1 data, we believe the mean change in total symptom score, together
with other measures of improvement in clinical outcomes, quality of
life and mast cell burden, will paint a compelling picture of
AYVAKIT clinical benefit, including its ability to modify the
disease biology and provide meaningful relief to patients living
with debilitating symptoms of non-advanced SM."
Highlights from AYVAKIT
Presentations at the EHA 2022 Congress
Three presentations at the EHA 2022 Congress will
highlight results from a study (NCT04695431) indirectly
comparing clinical outcomes in advanced SM patients receiving
AYVAKIT in the registrational EXPLORER and PATHFINDER trials,
versus patients treated with best available therapy in real-world
clinical practice. Results showed that AYVAKIT improved clinical
outcomes when retrospectively compared to best available therapies,
including the two other most common treatments (midostaurin,
cladribine) identified in the real-world study cohort.
"These rigorous, retrospective analyses highlight the prolonged
survival, extended duration of treatment and observed reduction in
mast cell burden shown by avapritinib in patients with advanced
systemic mastocytosis," said Prof. Dr. Andreas Reiter, M.D., University Medical Centre,
Heidelberg University, Mannheim, Germany. "Notably, in an indirect comparative
analysis of patients with SM and an associated hematologic
neoplasm, those treated in avapritinib clinical trials had a
significantly lower risk of death than those receiving prior best
available therapy in the real-world setting. These results are
highly meaningful for this patient population, which has a
significant disease burden and limited treatment options."
For this study, patients treated in real-world clinical practice
were identified in a retrospective medical chart review at six
centers with similar patient eligibility criteria as EXPLORER and
PATHFINDER. Retrospective data were collected and analyzed using
methods to balance key baseline variables; however, the study may
have limitations due to inherent differences between data collected
from prospective trials and real-world experience. No prospective,
randomized, controlled head-to-head studies have been conducted
comparing AYVAKIT to other therapies in patients with advanced SM.
EXPLORER and PATHFINDER results were reported as of an April 20, 2021 cutoff date.
Overall Survival
Data in Advanced SM
|
|
|
AYVAKIT1
|
Midostaurin
|
Cladribine
|
Number of
patients
|
176
|
94
|
44
|
Median in months (95%
CI)
|
NR (46.9,
NE)
|
28.6 (18.2,
44.6)
|
23.4 (14.8,
40.6)
|
Hazard ratio (95%
CI)2
|
---
|
HR: 0.59 (0.36,
0.97)
|
HR: 0.32 (0.15,
0.67)
|
P-value2
|
---
|
p<0.001
|
p=0.003
|
|
|
1.
|
Pooled data from
EXPLORER and PATHFINDER clinical trials of AYVAKIT in advanced SM
(all doses).
|
2.
|
Comparative analyses
used inverse-probability-of-treatment-weighting to balance
differences in key baseline covariates; HR<1 favors
AYVAKIT.
|
Additional weighted, indirect comparison analyses showed:
- AYVAKIT (all doses) reduced the risk of death by 58 percent
compared to best available therapy (p<0.001) in patients with SM
with an associated hematological neoplasm (SM-AHN).
- AYVAKIT (≤200 mg once-daily dose) reduced the risk of treatment
discontinuation by 64 percent compared to best available therapy
(p<0.001) in advanced SM patients.
- The maximum percent reduction in serum tryptase levels for
AYVAKIT (≤200 mg once-daily dose) was 85 percent, compared to 9
percent for best available therapy (p<0.001), in advanced SM
patients.
Regulatory approvals in the U.S. and EU were based on results
from the EXPLORER and PATHFINDER trials. In the U.S., AYVAKIT is
indicated for the treatment of adults with Advanced SM, including
aggressive SM (ASM), SM-AHN and mast cell leukemia (MCL). AYVAKIT
is not recommended for the treatment of patients with advanced SM
with low platelet counts (less than 50,000/µL). Warnings and
precautions include intracranial hemorrhage, cognitive effects and
embryo-fetal toxicity. The most common adverse reactions were
edema, diarrhea, nausea and fatigue/asthenia.
Further details from these analyses, along with additional SM
data, will be reported in multiple presentations at the EHA 2022
Congress:
- Overall survival in patients with advanced systemic
mastocytosis receiving avapritinib versus midostaurin or cladribine
(Abstract P1014)
- Overall survival in patients with systemic mastocytosis with
associated hematologic neoplasm treated with avapritinib versus
best available therapy (Abstract P1013)
- Duration of treatment and reduction in serum tryptase levels in
patients with advanced systemic mastocytosis treated with
avapritinib versus best available therapy (Abstract P1015)
- Responses to avapritinib in patients with advanced systemic
mastocytosis: histopathologic analyses from EXPLORER and PATHFINDER
clinical studies (Abstract P1027)
- Clinicopathologic and molecular correlates of organ damage
across the spectrum of advanced systemic mastocytosis (Abstract
P1038)
- Utility of KIT p.D816 in myeloid neoplasm without documented
systemic mastocytosis to detect hidden mast cells in bone marrow
(Abstract P996)
- HARBOR: A phase 2/3 study of BLU-263 in patients with indolent
systemic mastocytosis and monoclonal mast cell activation syndrome
(Trial-in-progress abstract P1017)
Tomorrow, June 10, copies of the posters will be available on
the EHA congress website and in the "Science―Publications and
Presentations" section of Blueprint Medicines' website.
Upcoming Investor
Conference
Kate Haviland, Chief Executive
Officer at Blueprint Medicines, will present a company overview at
the Jefferies Healthcare Conference today at 1:30 p.m. EDT. A live
webcast of the presentation will be available by visiting the
Investors & Media section of Blueprint Medicines' website at
http://ir.blueprintmedicines.com. A replay of the webcast will be
archived on Blueprint Medicines' website for 30 days following the
presentation.
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. Under the brand name AYVAKYT
(avapritinib), this medicine is approved by the European Commission
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.
AYVAKIT/AYVAKYT is not approved for the treatment of any other
indication in the U.S. or Europe.
Blueprint Medicines is developing AYVAKIT globally for the
treatment of advanced and non-advanced SM. The FDA granted
breakthrough therapy designation to AYVAKIT for the treatment
of moderate to severe indolent SM. The European Commission
granted orphan medicinal product designation for AYVAKYT for the
treatment of GIST and mastocytosis.
To learn about ongoing or planned clinical trials, contact
Blueprint Medicines in the U.S. at medinfo@blueprintmedicines.com
or +1 888-258-7768, or in Europe
at medinfoeurope@blueprintmedicines.com or +31 85 064 4001.
Additional information is available at blueprintclinicaltrials.com
and clinicaltrials.gov.
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
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 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. Monitor patients closely for risk of
ICH including those with thrombocytopenia, vascular aneurysm or a
history of ICH or cerebrovascular accident within the prior year.
Permanently discontinue AYVAKIT if ICH of any grade occurs. 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 adverse reactions can occur in patients receiving
AYVAKIT. Cognitive adverse reactions occurred in 39% of 749
patients and in 28% of 148 SM patients (3% were Grade >3).
Memory impairment occurred in 16% of patients; all events were
Grade 1 or 2. Cognitive disorder occurred in 10% of patients;
<1% of these events were Grade 3. Confusional state occurred in
6% of patients; <1% of these events were Grade 3. Other events
occurred in <2% of patients. Depending on the severity, withhold
AYVAKIT and then resume at same dose or at a reduced dose upon
improvement, or permanently discontinue.
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.
The most common adverse reactions (≥20%) at all doses were
edema, diarrhea, nausea, and fatigue/asthenia.
Avoid coadministration of AYVAKIT with strong and moderate CYP3A
inhibitors. If coadministration with a moderate CYP3A inhibitor
cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration
of AYVAKIT with strong and 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
www.fda.gov/medwatch.
Please click here to see the full Prescribing
Information for AYVAKIT.
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 OS is approximately 3.5 years in ASM, approximately two
years in SM-AHN and less than six months in
MCL.i In Europe, there are about 40,000 patients
with SM, and advanced SM represents about 5 to 10 percent of this
patient population.ii
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
symptomatic 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.iii,iv
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, timelines and expectations for interactions with
the FDA and other regulatory authorities; plans and timelines to
update the primary endpoint of the registrational PIONEER trial of
AYVAKIT in patients with non-advanced SM; expectations regarding
the potential benefits of AYVAKIT in treating patients with
non-advanced SM and advanced SM; 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 report
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 report, 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 and GAVRETO 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,
GAVRETO or any drug candidates it is developing; Blueprint
Medicines' ability to develop and commercialize companion
diagnostic tests for AYVAKIT/AYVAKYT, GAVRETO or any of its current
and future drug candidates; Blueprint Medicines' ability to
successfully expand its operations, research platform and portfolio
of therapeutic candidates, and the timing and costs thereof;
Blueprint Medicines' ability to realize the anticipated benefits of
its executive leadership transition plan; and the success of
Blueprint Medicines' current and future collaborations,
acquisitions, 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 report 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, GAVRETO and associated
logos are trademarks of Blueprint Medicines Corporation.
References
i Sperr WR, Kundi M, Alvarez-Twose I, et al.
International prognostic scoring system for mastocytosis (IPSM): a
retrospective cohort study. Lancet Haematol.
2019;6(12):e638-e649.
ii Estimated SM prevalence and patient subtypes based on
internal claims analysis and epidemiology reported in Orphanet
(orpha.net) and Cohen SS, Skovbo S, Vestergaard H, et al.
Epidemiology of systemic mastocytosis in Denmark. Br J Haemotol.
2014;166(4):521-528.
iii Jennings SV, Slee VM, Zack RM, et al. Patient
perceptions in mast cell disorders. Immunol Allergy Clin North
Am. 2018;38(3):505-525.
iv Mesa RA, Sullivan EM, Dubinski D, et al. Patient
reported outcomes among systemic mastocytosis (SM) patients in
routine clinical practice: results from the TouchStone Survey.
Blood. 2020;136(1):37.
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SOURCE Blueprint Medicines Corporation