CAMBRIDGE, Mass., Sept. 20, 2020 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC), a precision therapy company
focused on genomically defined cancers, rare diseases and cancer
immunotherapy, today announced results from the ongoing ARROW
clinical trial showing durable responses and a well-tolerated
safety profile for GAVRETO™ (pralsetinib) in patients with advanced
RET-mutant medullary thyroid cancer (MTC). In these registrational
data, GAVRETO demonstrated consistent clinical activity in patients
across lines of therapy and regardless of RET mutation genotypes,
including a high response rate in patients with gatekeeper
mutations resistant to multi-kinase inhibitors. The results are
being presented today in a proffered paper session during the
European Society for Medical Oncology (ESMO) Virtual Congress
2020.
"For patients with RET-mutant medullary thyroid cancer, there is
an important need for targeted therapies like pralsetinib (GAVRETO)
that are highly active across RET genotypes, including gatekeeper
resistance mutations," said Mimi Hu,
M.D., professor in the Department of Endocrine Neoplasia and
Hormonal Disorders at The University of
Texas MD Anderson Cancer Center. "The reported data
highlight the robust clinical activity and safety of GAVRETO, with
most patients remaining on treatment for prolonged periods of time.
These results are a promising advancement for RET-mutant medullary
thyroid cancer across both systemic treatment-naïve and previously
treated patients."
"By selectively inhibiting RET alterations, GAVRETO has broad
potential to address the limitations of multi-kinase inhibitors and
enable transformative outcomes for patients with RET-mutant
medullary thyroid cancer," said Andy
Boral, M.D., Ph.D., Chief Medical Officer at Blueprint
Medicines. "Across first-line and previously treated settings,
GAVRETO has shown durable clinical benefits and a well-tolerated
safety profile that has remained consistent over time. With the
recent FDA approval of GAVRETO in patients with RET fusion-positive
metastatic non-small cell lung cancer, these data further support
our efforts to bring this once-daily treatment to patients across
multiple RET-driven tumor types."
As previously announced, the U.S. Food and Drug Administration
(FDA) has accepted a new drug application (NDA) for GAVRETO for the
treatment of patients with advanced or metastatic RET-mutant MTC
and RET fusion-positive thyroid cancer. This NDA was accepted for
priority review under the FDA's Real-Time Oncology Review (RTOR)
pilot program, which aims to explore a more efficient review
process to ensure safe and effective treatments are available to
patients as early as possible.
In addition, Blueprint Medicines today announced that the
National Comprehensive Cancer Network has updated its Clinical
Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer
(NSCLC) to include GAVRETO as a preferred treatment option
(category 2A) for patients with RET fusion-positive NSCLC as a
first-line or subsequent therapy. This rating indicates that there
is uniform NCCN consensus that the intervention is appropriate. The
NCCN Guidelines are the recognized clinical standard for cancer
care by U.S. healthcare providers and payers, and are maintained by
a committee of expert physicians from leading U.S. cancer
centers.
GAVRETO is being jointly commercialized
by Genentech, a wholly owned member of the Roche Group, and
Blueprint Medicines in the U.S. and will be commercialized by Roche
outside of the U.S., excluding Greater
China (Mainland China, Hong
Kong, Macau and
Taiwan).
Highlights from the ARROW Trial in Patients with RET-Mutant
MTC
The presented data included response-evaluable patients with
RET-mutant MTC who were previously treated with cabozantinib or
vandetanib, or naïve to systemic treatment. Tumor response was
assessed by blinded, independent central review using Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1. All
patients received a GAVRETO starting dose of 400 mg once daily
(QD), and results were reported as of a data cutoff date of
February 13, 2020.
GAVRETO demonstrated broad clinical activity in patients with
RET-mutant MTC with or without prior systemic therapy. In 53
patients previously treated with cabozantinib or vandetanib, the
overall response rate (ORR) was 60 percent (95% CI: 46%, 74%) with
one response pending confirmation, and the disease control rate
(DCR) was 96 percent (95% CI: 87%, 100%). The median duration of
response (DOR) was not reached (95% CI: not reached, not reached),
with 94 percent of responders remaining on treatment. The median
progression-free survival (PFS) was not reached (95% CI: not
reached, not reached) in patients previously treated with
cabozantinib or vandetanib.
In 19 systemic treatment-naïve patients who were ineligible for
standard therapy per the study protocol, the confirmed ORR was 74
percent (95% CI: 49%, 91%), and the DCR was 100 percent (95% CI:
82%, 100%). The median DOR was not reached (95% CI: 7 months, not
reached), with 93 percent of responders remaining on treatment. The
median PFS was not reached (95% CI: not reached, not reached) in
systemic treatment-naïve patients.
Five of six patients whose tumors had a RET V804M or V804L
gatekeeper mutation achieved a clinical response. Three patients
previously treated with multi-kinase inhibitors had a RET M918T
activating mutation and a RET V804M or V804L gatekeeper resistance
mutation at baseline, and all three of these patients had a
clinical response following GAVRETO treatment.
The reported safety data included a total of 438 patients
enrolled in the ARROW trial at a GAVRETO starting dose of 400 mg
QD, regardless of tumor type. GAVRETO was well-tolerated with
safety results consistent with previously reported data. Overall,
treatment-related adverse events (AEs) were primarily Grade 1 or 2.
The most common treatment-related AEs reported by investigators
(≥15 percent) were increased aspartate aminotransferase, anemia,
increased alanine aminotransferase, hypertension, constipation,
decreased white blood cell count, neutropenia, decreased neutrophil
count and hyperphosphatemia. Investigator-reported Grade 3 or
higher treatment-related AEs (≥5 percent) were hypertension,
neutropenia, anemia and decreased neutrophil count. Four percent of
patients discontinued GAVRETO due to treatment-related AEs.
These data for GAVRETO are being reported in a proffered paper
(Abstract Number: 1913O) at the ESMO Virtual Congress 2020. A copy
of the data presentation is available in the "Science—Publications
and Presentations" section of Blueprint Medicines' website at
www.BlueprintMedicines.com.
About RET-Altered Solid Tumors
RET activating fusions and mutations are key disease drivers in
many cancer types, including NSCLC and multiple types of thyroid
cancer. RET fusions are implicated in approximately 1 to 2 percent
of patients with NSCLC and approximately 10 to 20 percent of
patients with papillary thyroid cancer, while RET mutations are
implicated in approximately 90 percent of patients with advanced
MTC. In addition, oncogenic RET fusions are observed at low
frequencies in colorectal, breast, pancreatic and other cancers, as
well as in patients with treatment-resistant EGFR-mutant NSCLC.
About the ARROW Trial
The Phase 1/2 ARROW trial (ClinicalTrials.gov Identifier: NCT03037385)
is designed to evaluate the safety, tolerability and efficacy of
GAVRETO in adults with RET-altered cancers. The trial consists of
two parts: a dose escalation portion, which is complete, and an
expansion portion in patients treated at 400 mg QD. The study's
objectives include assessing response, pharmacokinetics,
pharmacodynamics and safety. The trial is enrolling patients at
multiple sites in the United
States, European Union and Asia.
Patients and physicians interested in the ARROW trial can
contact the Blueprint Medicines study director at
medinfo@blueprintmedicines.com or 1-888-BLU-PRNT (1-888-258-7768)
in the U.S., or medinfoeurope@blueprintmedicines.com or +31 85 064
4001 in Europe. Additional
information is available at www.BlueprintClinicalTrials.com/ARROW
and www.clinicaltrials.gov.
About GAVRETO (pralsetinib)
GAVRETO (pralsetinib) is a once-daily oral targeted therapy
approved by the FDA for the treatment of adults with metastatic RET
fusion-positive NSCLC as detected by an FDA approved test. It
is designed to selectively and potently target oncogenic RET
alterations. In pre-clinical studies, GAVRETO inhibited RET at
lower concentrations than other pharmacologically relevant kinases,
including VEGFR2, FGFR2 and JAK2. For more information, visit
GAVRETO.com.
GAVRETO is not approved for the treatment of any other
indication in the U.S. by the FDA or for any indication in any
other jurisdiction by any other health authority.
Blueprint Medicines and Roche are co-developing GAVRETO globally
(excluding Greater China) for the
treatment of patients with RET-altered NSCLC, various types of
thyroid cancer and other solid tumors. The FDA has accepted an NDA
for GAVRETO for the treatment of RET-mutant MTC and RET
fusion-positive thyroid cancer, and the European Medicines Agency
has validated a marketing authorization application for GAVRETO for
the treatment of RET fusion-positive NSCLC. The FDA has granted
breakthrough therapy designation to GAVRETO for the treatment of
RET fusion-positive NSCLC that has progressed following
platinum-based chemotherapy and for RET mutation-positive MTC that
requires systemic treatment and for which there are no acceptable
alternative treatments.
Blueprint Medicines has an exclusive collaboration and license
agreement with CStone Pharmaceuticals for the development and
commercialization of GAVRETO in Greater
China.
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 two FDA-approved precision therapies 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 plans and timelines for the development and, if approved,
commercialization of GAVRETO for the treatment of patients with
RET-mutant MTC, RET fusion-positive thyroid cancer and other
RET-altered cancers; the potential benefits of the FDA's RTOR
program; the potential benefits of Blueprint Medicines'
current and future approved drugs or drug candidates in treating
patients; 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™ (avapritinib) and GAVRETO; 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 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,
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.
Trademarks
Blueprint Medicines, GAVRETO, AYVAKIT and associated logos are
trademarks of Blueprint Medicines Corporation.
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