CAMBRIDGE, Mass., Jan. 8, 2020 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC), a precision therapy company
focused on genomically defined cancers, rare diseases and cancer
immunotherapy, today announced independent centrally reviewed
top-line data for pralsetinib in patients with RET fusion-positive
non-small cell lung cancer (NSCLC). The data from the ongoing Phase
1/2 ARROW clinical trial of pralsetinib showed a 61 percent
objective response rate (ORR) and prolonged durability, with a
median duration of response (DOR) not reached, in patients with RET
fusion-positive NSCLC previously treated with platinum-based
chemotherapy. Designed by Blueprint Medicines, pralsetinib is a
potent and highly selective once-daily oral inhibitor of RET
fusions and mutations, including predicted resistance
mutations.
In addition, Blueprint Medicines announced it has initiated the
submission of a rolling New Drug Application (NDA) to the U.S. Food
and Drug Administration (FDA) for pralsetinib for the treatment of
patients with RET fusion-positive NSCLC. The company expects to
complete the NDA submission in the first quarter of 2020.
Blueprint Medicines also plans to submit an NDA to the FDA for
pralsetinib for the treatment of patients with medullary thyroid
cancer (MTC) previously treated with an approved multi-kinase
inhibitor in the second quarter of 2020.
"As the clinical data for pralsetinib have matured, with deep
and durable responses along with robust evidence of activity
against brain metastases, our confidence has continued to grow in
the potential of pralsetinib to provide lasting benefit to a broad
population of patients with RET fusion-positive NSCLC, including
those with newly diagnosed unresectable or metastatic disease,"
said Andy Boral, M.D., Ph.D., Chief
Medical Officer of Blueprint Medicines. "Now, with strong,
centrally reviewed top-line data, we feel a profound sense of
urgency and have taken the first step toward making pralsetinib
broadly available to patients by initiating a rolling NDA
submission to the FDA."
Top-line Data from Phase 1/2 ARROW Trial in RET
Fusion-Positive NSCLC
Results from the Phase 1/2 ARROW clinical trial of pralsetinib
will be used to support the NDA submission for pralsetinib for the
treatment of patients with RET fusion-positive NSCLC. The
registration endpoints are ORR and DOR based on independent central
radiology and Response Evaluation Criteria in Solid Tumors version
1.1 (RECIST 1.1) criteria.
Top-line efficacy data were reported for patients treated with
pralsetinib who were evaluable for response assessment per RECIST
1.1, as determined by blinded independent central review. All
patients received the proposed indicated dose of 400 mg once daily
(QD).
In 80 patients with RET fusion-positive NSCLC previously treated
with platinum-based chemotherapy, the ORR was 61 percent (95% CI:
50-72%) per independent central review (two responses pending
confirmation) as of a data cutoff date of November 18, 2019. Overall, 95 percent of
patients had tumor shrinkage, including 14 percent of patients with
complete regression of target tumors. The median DOR was not
reached (95% CI: 11.3 months, not estimable).
In 26 patients with treatment-naïve RET fusion-positive NSCLC,
the ORR was 73 percent (95% CI: 52-88%) per independent central
review (all responses confirmed), with 12 percent of patients
achieving a complete response. All patients had tumor
shrinkage.
Top-line safety data were consistent with those previously
reported. Pralsetinib was well-tolerated, and most adverse events
(AEs) were Grade 1 or 2. Across all patients enrolled in the ARROW
trial treated with the proposed indicated dose of 400 mg QD
(N=354), only four percent of patients discontinued treatment with
pralsetinib due to treatment-related AEs.
Blueprint Medicines plans to present the full registration
dataset at a scientific meeting later this year.
Planned Phase 3 AcceleRET Lung Trial in Treatment-Naïve RET
Fusion NSCLC
In addition, Blueprint Medicines plans to initiate the first
clinical trial site for its Phase 3 AcceleRET Lung clinical trial
in January 2020. The primary
objective of the AcceleRET trial is to evaluate the potential of
pralsetinib to extend progression free survival (PFS) compared to
platinum-based chemotherapy with or without pembrolizumab in
patients with first-line RET fusion-positive NSCLC.
The global, randomized AcceleRET trial will enroll approximately
250 patients with advanced or metastatic RET fusion-positive NSCLC
who have received no prior systemic therapy for metastatic disease.
Participants will be randomized to receive either pralsetinib or
the investigator's choice of platinum-based chemotherapy regimen
with or without pembrolizumab. The trial's primary endpoint is PFS
and secondary endpoints include overall survival, ORR and DOR.
Patients may receive local testing to identify a RET fusion. In
addition, patients randomized to the control arm may crossover upon
progression to receive pralsetinib. Multiple trial sites are
planned in North America,
Europe and Asia.
About RET-Altered Solid Tumors
RET activating fusions and mutations are key disease drivers in
many cancer types, including NSCLC and MTC. 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 (PTC), while RET mutations are implicated in
approximately 90 percent of patients with advanced MTC. In
addition, oncogenic RET alterations are observed at low frequencies
in colorectal, breast, pancreatic and other cancers, and RET
fusions have been observed in patients with treatment-resistant,
EGFR-mutant NSCLC.
Currently, there are no approved therapies that selectively
target RET-driven cancers, although there are several approved
multi-kinase inhibitors (MKIs) with RET activity being evaluated in
clinical trials. To date, clinical activity attributable to RET
inhibition has been uncertain for these approved MKIs, likely due
to insufficient inhibition of RET and off-target toxicities. There
is a need for precision therapies that provide durable clinical
benefit by selectively targeting RET alterations and anticipated
resistance mutations.
About Pralsetinib
Pralsetinib is an investigational, once-daily oral precision
therapy specifically designed for highly potent and selective
targeting of oncogenic RET alterations. Blueprint Medicines is
developing pralsetinib for the treatment of patients with
RET-altered NSCLC, MTC and other solid tumors. The FDA has granted
Breakthrough Therapy Designation to pralsetinib for the treatment
of RET-fusion positive NSCLC that has progressed following
platinum-based chemotherapy, and RET-mutant MTC that requires
systemic treatment and for which there are no acceptable
alternative treatments.
Pralsetinib was designed by Blueprint Medicines' research team,
leveraging the company's proprietary compound library. In
preclinical studies, pralsetinib consistently demonstrated
sub-nanomolar potency against the most common RET fusions,
activating mutations and predicted resistance mutations. In
addition, pralsetinib demonstrated markedly improved selectivity
for RET compared to pharmacologically relevant kinases, including
approximately 90-fold improved potency for RET versus VEGFR2. By
suppressing primary and secondary mutants, pralsetinib has the
potential to overcome and prevent the emergence of clinical
resistance. Blueprint Medicines believes this approach will enable
durable clinical responses across a diverse range of RET
alterations, with a favorable safety profile.
Blueprint Medicines has an exclusive collaboration and license
agreement with CStone Pharmaceuticals for the development and
commercialization of pralsetinib, avapritinib and fisogatinib in
Mainland China, Hong Kong,
Macau and Taiwan. Blueprint Medicines retains
development and commercial rights for all three drug candidates in
the rest of the world.
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 are currently advancing three investigational
medicines in clinical development, along with multiple 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 of its drug
candidates, including the timing, design, implementation,
enrollment, plans and announcement of results regarding Blueprint
Medicines' ongoing and planned clinical trials for pralsetinib;
plans, timelines and expectations for full data from the ARROW
clinical trial; expectations regarding the potential benefits of
pralsetinib in treating patients with RET-altered NSCLC, MTC and
other solid tumors; plans and timelines for submitting and
completing ongoing and planned marketing applications for
pralsetinib; plans, timelines and expectations for interactions
with the FDA and other regulatory authorities; 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 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.
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