CAMBRIDGE, Mass., Jan. 9, 2020 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC), a precision therapy company
focused on genomically defined cancers, rare diseases and cancer
immunotherapy, today announced that the U.S. Food and Drug
Administration (FDA) has approved AYVAKIT™ (avapritinib) for the
treatment of adults with unresectable or metastatic
gastrointestinal stromal tumor (GIST) harboring a platelet-derived
growth factor receptor alpha (PDGFRA) exon 18 mutation, including
PDGFRA D842V mutations. AYVAKIT is the first precision therapy
approved to treat a genomically defined population of patients with
GIST.
The FDA granted a full approval to AYVAKIT based on efficacy
results from the Phase 1 NAVIGATOR clinical trial, as well as
combined safety results from multiple clinical trials for
avapritinib. In patients with PDGFRA exon 18 mutant GIST, AYVAKIT
had an overall response rate (ORR) of 84 percent (95% CI: 69%,
93%), and a median duration of response (DOR) was not reached. The
most common adverse reactions (≥20 percent) were edema, nausea,
fatigue/asthenia, cognitive impairment, vomiting, decreased
appetite, diarrhea, hair color changes, increased lacrimation,
abdominal pain, constipation, rash and dizziness. Blueprint
Medicines plans to make AYVAKIT available in the U.S. within a
week.
GIST is a rare, genomically driven sarcoma of the
gastrointestinal (GI) tract. Approximately 6 percent of patients
with newly diagnosed GIST have PDGFRA exon 18 mutations. The most
common PDGFRA exon 18 mutation is the D842V mutation, which is
resistant to all other approved therapies. A retrospective study
showed that when these patients were treated with imatinib, they
had an ORR of 0 percent.2
"Today's approval of AYVAKIT brings forward a new standard of
care for patients with PDGFRA exon 18 mutant GIST, a genomically
defined population that previously had very limited treatment
options. For the first time, we can offer these patients a highly
effective treatment that targets the underlying genetic cause of
their disease," said Michael
Heinrich, M.D., Professor of Medicine at Oregon Health &
Science University and an investigator on the NAVIGATOR trial.
"Building on our growing understanding of the molecular basis of
GIST, this milestone ushers in a new era of precision medicine in
this disease. The FDA approval represents a call to action to
conduct mutational testing in all patients with GIST before
initiating kinase inhibitor therapy, as recommended by clinical
guidelines, so appropriate patients may realize the benefits of
this promising new medicine."
"The full approval of AYVAKIT based on robust data from our
Phase 1 NAVIGATOR clinical trial is an incredibly exciting
milestone for our company and, more importantly, for GIST patients
with a PDGFRA exon 18 mutation, who have been waiting for a new
treatment option," said Jeff Albers,
Chief Executive Officer at Blueprint Medicines. "AYVAKIT is the
first of what we hope will be many approved medicines enabled by
our research platform. Now, as we begin to deliver AYVAKIT to
patients and their healthcare providers, we aim to fortify our
leadership in the field of precision medicine and build a
foundation for our broader portfolio by pairing our strong research
and development capabilities with an equally talented commercial
organization focused on addressing patient needs, accelerating
diagnostic testing and enabling access."
Blueprint Medicines is dedicated to helping patients with PDGFRA
exon 18 mutant GIST access treatment with AYVAKIT and providing
robust support throughout their treatment journey. As part of this
commitment, Blueprint Medicines is introducing YourBlueprint™, a
patient support program that offers access and affordability
solutions for individuals receiving AYVAKIT. For more information,
visit YourBlueprint.com or call 1-888-BLUPRNT
(1-888-258-7768), Monday to Friday, 8:00
a.m. to 8:00 p.m. ET. Healthcare providers who prescribe
AYVAKIT can fill out an enrollment form at
YourBlueprint.com/HCP to help patients access Blueprint
Medicines' support services.
Conference Call Information
Blueprint Medicines will host a live webcast beginning
at 4:30 p.m. ET today to discuss the FDA approval of AYVAKIT.
To access the live call, please dial (855) 728-4793 (domestic) or
(503) 343-6666 (international), and refer to conference ID
5579052. A webcast of the conference call will be available in
the Investors & Media section of Blueprint Medicines' website
at http://ir.blueprintmedicines.com. The archived webcast will be
available on Blueprint Medicines' website approximately two
hours after the conference call and will be available for 90 days
following the call.
Update on New Drug Application for the Treatment of
Fourth-Line GIST
Blueprint Medicines today announced that the FDA
administratively split the proposed indications for avapritinib
under the initial New Drug Application (NDA) into two separate
NDAs: one for PDGFRA exon 18 mutant GIST, which the FDA approved
today, and one for fourth-line GIST. The Prescription Drug User Fee
Act (PDUFA) action date for the fourth-line GIST indication is
currently February 14, 2020. As
previously announced, for the NDA for fourth-line GIST an extension
of up to three months for the PDUFA action date will likely be
required to enable Blueprint Medicines to provide top-line data to
the FDA from VOYAGER, a Phase 3 clinical trial evaluating
avapritinib versus regorafenib in third- or fourth-line GIST.
AYVAKIT Efficacy and Safety Data1
The efficacy of AYVAKIT was established from 43 patients in the
NAVIGATOR trial with unresectable or metastatic GIST harboring
PDGFRA exon 18 mutations, including 38 patients with PDGFRA D842V
mutations. These patients were treated at starting doses of either
300 mg once daily (QD) or 400 mg QD. Efficacy data were evaluated
by blinded, independent central radiology review, based on modified
Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST
1.1 criteria) for GIST. The recommended dose of AYVAKIT is 300 mg
QD. AYVAKIT is available in 100 mg, 200 mg and 300 mg dose
strengths.
AYVAKIT demonstrated durable responses in patients with PDGFRA
exon 18 mutations across multiple lines of treatment. In these
patients, the ORR was 84 percent [7 percent complete responses
(CR), 77 percent partial responses (PR)]. In patients with PDGFRA
D842V mutations, the ORR was 89 percent (95% CI: 75%, 97%; 8
percent CR, 82 percent PR). The median DOR was not reached in
either patient population (range: 1.9+ months, 20.3+ months).
The safety of AYVAKIT in patients with unresectable or
metastatic GIST was evaluated in 204 patients who received 300 mg
QD or 400 mg QD dosing in the NAVIGATOR trial. Patients were
heavily pre-treated, with patients receiving a median of three
prior kinase inhibitors (range: 0 to 7).
There are no contraindications for AYVAKIT. AYVAKIT has warnings
and precautions of intracranial hemorrhage, central nervous system
effects and embryo-fetal toxicity. The most common adverse
reactions (≥20 percent) were edema, nausea, fatigue/asthenia,
cognitive impairment, vomiting, decreased appetite, diarrhea, hair
color changes, increased lacrimation, abdominal pain, constipation,
rash and dizziness.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA
for the treatment of adults with unresectable or metastatic GIST
harboring a PDGFRA exon 18 mutation, including PDGFRA D842V
mutations. AYVAKIT is a selective and potent inhibitor of KIT and
PDGFRA mutant kinases. It is the only FDA-approved type 1 inhibitor
for GIST that works by directly binding to the active kinase
conformation from which mutant KIT and PDGFRA signal. AYVAKIT has
demonstrated inhibition of a broad range of KIT and PDGFRA
mutations associated with GIST, including potent clinical activity
against activation loop mutations that are associated with
resistance to currently approved therapies. For more information,
visit AYVAKIT.com.
Avapritinib is not approved for the treatment of any other
indication in the U.S. or any other jurisdiction by the FDA or any
other health authority.
Blueprint Medicines is pursuing a broad clinical development
program for avapritinib across multiple lines of GIST treatment, as
well as for advanced, smoldering and indolent systemic mastocytosis
(SM). The FDA has granted Breakthrough Therapy Designation to
avapritinib for two indications: one for the treatment of
unresectable or metastatic GIST harboring the PDGFRA D842V mutation
and one for the treatment of advanced SM, including the subtypes of
aggressive SM, SM with an associated hematologic neoplasm and mast
cell leukemia. For more information about avapritinib clinical
trials, visit www.clinicaltrials.gov or
www.blueprintclinicaltrials.com.
About GIST
GIST is a sarcoma, or tumor of bone or connective tissue, of the
GI tract. Tumors arise from cells in the wall of the GI tract and
occur most often in the stomach or small intestine. Most patients
are diagnosed between the ages of 50 to 80, and diagnosis is
typically triggered by GI bleeding, incidental findings during
surgery or imaging and, in rare cases, tumor rupture or GI
obstruction.
Most GIST cases are caused by mutations in KIT or PDGFRA that
force protein kinases into an increasingly active state. Because
other available therapies primarily bind to the inactive protein
conformations, certain primary and secondary mutations typically
result in treatment resistance and lead to disease progression.
In unresectable or metastatic GIST, clinical benefits from
existing treatments can vary by mutation type. Mutational testing
is critical to tailor therapy to the underlying disease driver and
is recommended in expert guidelines. Currently, there are no
approved therapies for patients with KIT-driven GIST whose disease
progresses beyond imatinib, sunitinib and regorafenib. In patients
with advanced PDGFRA D842V-driven GIST treated with imatinib, a
retrospective study showed an ORR of 0 percent.2
Important Safety Information
Intracranial hemorrhage (e.g., subdural hematoma, intracranial
hemorrhage, and cerebral hemorrhage) occurred in 1% of 267 patients
(0.7% Grade 3 or 4) with GIST and overall in 3% of 335 patients
(1.2% Grade 3 or 4) who received AYVAKIT. Overall, 0.9% of patients
receiving AYVAKIT required permanent discontinuation for an
intracranial hemorrhage. Withhold AYVAKIT and then resume at a
reduced dose upon resolution, or permanently discontinue AYVAKIT
based on severity.
In 335 patients receiving AYVAKIT, CNS adverse reactions
occurred overall in 58% of patients including cognitive impairment
(41%; 3.6% Grade 3 or 4), dizziness (20%; 0.6% Grade 3 or 4), sleep
disorders (15%; 0.3% Grade 3 or 4), mood disorders (13%; 1.5% Grade
3 or 4), speech disorders (6%; none Grade 3 or 4), and
hallucinations (2.1%; none Grade 3 or 4). Overall, 3.9% of patients
required permanent discontinuation of AYVAKIT for a CNS adverse
reaction. Depending on severity, withhold AYVAKIT and then resume
at the same dose or at a reduced dose upon improvement, or
permanently discontinue AYVAKIT.
AYVAKIT can cause fetal harm when administered to a pregnant
woman. Advise females of reproductive potential and 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 two weeks after the final dose. Advise females and
males of reproductive potential that AYVAKIT may impair
fertility.
In 204 patients with unresectable or metastatic GIST, the most
common adverse reactions (≥ 20%) were edema, nausea,
fatigue/asthenia, cognitive impairment, vomiting, decreased
appetite, diarrhea, hair color changes, increased lacrimation,
abdominal pain, constipation, rash and dizziness.
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.
Please click here to see the full Prescribing
Information for AYVAKIT.
About Blueprint Medicines
Blueprint Medicines is a precision therapy company striving
to improve human health. With a focus on genomically defined
cancers, rare diseases and cancer immunotherapy, we are developing
transformational medicines rooted in our leading expertise in
protein kinases, which are proven drivers of disease. Our uniquely
targeted, scalable approach empowers the rapid design and
development of new treatments and increases the likelihood of
clinical success. We have one FDA-approved precision therapy and
are currently advancing multiple investigational medicines in
clinical development, along with a number of research programs. 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 approval
of AYVAKIT and the implications of such approval for patients,
caregivers and healthcare professionals; expectations concerning
when AYVAKIT will be commercially available in the U.S.; Blueprint
Medicines' plans and ability to provide robust support services for
patients prescribed AYVAKIT through YourBlueprint; plans, timelines
and expectations for interactions with the FDA and other regulatory
authorities; plans, timelines and expectations related to the NDA
for fourth-line GIST and any extension of the PDUFA action date;
and Blueprint Medicines' strategy, goals and anticipated
milestones, business plans and focus. The words "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 plan in
establishing a commercial infrastructure, and successfully
launching, marketing and selling its approved product; Blueprint
Medicines' ability to successfully expand the indication for
AYVAKIT in the future; the delay of any current or planned clinical
trials or the development of Blueprint Medicines' drug candidates
or licensed product candidate; 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; 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 or licensing arrangements, including its
cancer immunotherapy collaboration with F. Hoffmann-La Roche Ltd
and Hoffmann-La Roche Inc., its collaboration with CStone
Pharmaceuticals and its license to Clementia Pharmaceuticals. 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 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.
References
1 AYVAKIT™ (avapritinib) Prescribing Information
(U.S.). Blueprint Medicines Corporation, Cambridge, Massachusetts, USA; January 2020.
2 Cassier PA, Fumagalli E, Rutkowski P., et al.
Outcome of patients with platelet-derived growth factor receptor
alpha-mutated gastrointestinal stromal tumors in the tyrosine
kinase inhibitor era. Clin Cancer
Res. 2012;18(16):4458-4464.
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