CAMBRIDGE, Mass., Dec. 6, 2021 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC) today announced two Nature
Medicine publications on the registration-enabling EXPLORER and
PATHFINDER trials of AYVAKIT® (avapritinib), highlighting its
robust efficacy and safety datasets in advanced systemic
mastocytosis (Advanced SM). The publications feature overall
response, patient-reported outcomes and survival data, which
reinforce the durable activity of AYVAKIT. Additional new analyses
underscore the treatment's impact regardless of patient subgroup or
disease pathology. Based on these data, AYVAKIT was approved by the
U.S. Food and Drug Administration (FDA) for the treatment of adults
with advanced SM in June 2021.
SM is a rare hematologic disorder driven by the KIT D816V
mutation in nearly all cases. In advanced SM, the median overall
survival with previously available treatment options ranges from
less than six months to approximately 3.5 years, depending on the
subtype.1
"Targeting the primary genetic driver of systemic mastocytosis,
avapritinib has shown rapid and durable improvements in mast cell
burden, patient-reported symptoms and quality of life, with a
generally well-tolerated safety profile," said Daniel DeAngelo, M.D., Ph.D., Chief of the
Division of Leukemia at Dana-Farber Cancer Institute, lead and
senior author on the EXPLORER and PATHFINDER trial publications,
respectively. "I am highly encouraged by the survival benefits
observed with this therapy, including in patients with mast cell
leukemia who have a particularly poor prognosis. The depth of
activity achieved by avapritinib, including molecular remission of
KIT D816V, sets a new benchmark for the treatment of advanced
systemic mastocytosis."
"The data published today in Nature Medicine comprise the
largest therapeutic dataset ever reported in advanced systemic
mastocytosis, encompassing two studies enrolling approximately 150
patients with up to four years of follow-up, and reflecting our
deep commitment to pioneer new science and improve outcomes for
patients living with this devastating disease," said Becker Hewes,
M.D., Chief Medical Officer at Blueprint Medicines.
In addition, Blueprint Medicines announced plans to report four
SM data presentations, including an oral presentation on the
EXPLORER trial, at the 63rd American Society of
Hematology (ASH) Annual Meeting and Exposition in Atlanta on December
11-14, 2021. These datasets further illustrate the
significant impact of AYVAKIT in advanced SM, showcase Blueprint
Medicines' clinical leadership in SM and reflect the company's
ongoing collaboration with the community to improve patient
care.
Nature Medicine Publication Highlights
Across the EXPLORER and PATHFINDER studies, 148 patients with
advanced SM were enrolled as of the data cutoff dates. Treatment
response was evaluated using modified IWG-MRT-ECNM criteria, with
the overall response rate defined as complete remission with full
or partial recovery of peripheral blood counts, partial remission
or clinical improvement. All responses were confirmed. The results
were reported as of a data cutoff date of May 27, 2020 for the EXPLORER trial and
June 23, 2020 for the PATHFINDER
trial.
|
EXPLORER
|
PATHFINDER
|
Response evaluable
patients
|
n=53
|
n=32
|
Overall response
rate
|
75% (95% CI: 62%,
86%)
|
75% (95% CI: 57%,
89%)
|
Median duration of
response
|
38 months (95% CI, 22
months, NEa)
|
NEa (95%
CI: NEa, NEa)
|
Overall
survival
|
76% estimated
24-month rate
|
86% estimated
12-month rate
|
Note: (a) NE, not estimable.
- Across both studies, statistically significant improvements in
patient-reported symptoms were observed, as measured by the
Advanced SM Symptom Assessment Form Total Symptom Score.
- AYVAKIT showed broad activity across all advanced SM subtypes,
including SM with an associated hematological neoplasm (SM-AHN).
For example, substantial reductions were observed in monocytosis in
patients with SM and chronic myelomonocytic leukemia, and in
eosinophilia in patients with SM and chronic eosinophilic leukemia,
potentially reflecting the multi-lineage involvement of the KIT
D816V mutation.
AYVAKIT was generally well-tolerated, and most adverse events
(AEs) were Grade 1 or 2. The most common AEs included edema,
thrombocytopenia, anemia, diarrhea, nausea, fatigue, vomiting,
neutropenia, headache, cognitive effects and abdominal pain.
Overall, 10 percent of patients in the EXPLORER trial and 5 percent
of patients in the PATHFINDER trial discontinued AYVAKIT due to
treatment-related AEs. AYVAKIT is not recommended for the treatment
of patients with advanced SM with low platelet counts (less than
50,000/µL), which is consistent with current patient eligibility
criteria in the EXPLORER and PATHFINDER trials.
The papers, titled "Safety and efficacy of avapritinib in
advanced systemic mastocytosis: the phase 1 EXPLORER trial," and
"Efficacy and safety of avapritinib in advanced systemic
mastocytosis: interim analysis of the phase 2 PATHFINDER trial,"
were published online in Nature Medicine on December 6, 2021.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA
for the treatment of two indications: adults with Advanced SM,
including aggressive SM (ASM), SM-AHN and mast cell leukemia (MCL),
and adults with unresectable or metastatic gastrointestinal stromal
tumors (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 unresectable or
metastatic GIST harboring the PDGFRA D842V mutation, and in
Mainland China (AYVAKIT®) for the treatment of adults with
unresectable or metastatic PDGFRA exon 18 mutant GIST.
AYVAKIT/AYVAKYT is not approved for the treatment of any other
indication in the U.S., Europe or
Greater China, or for any
indication in any other jurisdiction by any other health
authority.
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
advanced SM, including the subtypes of ASM, SM-AHN and MCL, and for
the treatment of moderate to severe indolent SM.
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 clinicaltrials.gov.
Blueprint Medicines has an exclusive collaboration and license
agreement with CStone Pharmaceuticals for the development and
commercialization of AYVAKIT in Greater
China, which encompasses Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains
development and commercial rights for AYVAKIT in the rest of the
world.
About SM
SM is a rare disease 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.
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.
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 Blueprint Medicines
Blueprint Medicines is a global precision therapy company that
invents life-changing medicines for people with cancer and
hematologic disorders. Applying an approach that is both precise
and agile, we create therapies 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 genomically defined cancers, systemic mastocytosis,
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, expectations
regarding the potential benefits of AYVAKIT in treating patients
with 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 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 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 establishing a commercial infrastructure, and successfully
launching, marketing and selling current or future approved
products, including AYVAKIT and GAVRETO®
(pralsetinib); Blueprint Medicines' ability to
successfully expand the approved indications for AYVAKIT and
GAVRETO or obtain marketing approval for AYVAKIT and GAVRETO 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
pre-clinical and clinical results for Blueprint
Medicines' drug candidates, which may not support further
development of such drug candidates; actions of regulatory
agencies, which may affect the initiation, timing and progress of
clinical trials; Blueprint Medicines' ability to develop
and commercialize companion diagnostic tests for its current and
future drug candidates; and the success of Blueprint
Medicines' current and future collaborations, partnerships or
licensing arrangements, including Blueprint
Medicines' global collaboration with Roche for the development
and commercialization of GAVRETO. 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.
Reference
1 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.
Trademarks
Blueprint Medicines, AYVAKIT, AYVAKYT, GAVRETO and associated
logos are trademarks of Blueprint Medicines Corporation.
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