CAMBRIDGE, Mass., Dec. 1, 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 GAVRETO™ (pralsetinib) for the
treatment of patients with RET-altered thyroid cancers. The
accelerated approval expands the labeled indications for GAVRETO to
include adult and pediatric patients 12 years of age and older with
advanced or metastatic RET-mutant medullary thyroid cancer (MTC)
who require systemic therapy, or with advanced or metastatic RET
fusion-positive thyroid cancer who require systemic therapy and who
are radioactive iodine-refractory (if radioactive iodine is
appropriate). Developed by Blueprint Medicines, GAVRETO is a
once-daily oral precision therapy designed to potently and
selectively target RET alterations that drive multiple tumor types.
GAVRETO is jointly commercialized in the U.S. by Blueprint
Medicines and Genentech, a wholly owned member of the Roche Group,
under Blueprint Medicines' collaboration with Roche.
In the Phase 1/2 ARROW trial, GAVRETO showed durable efficacy
and was generally well-tolerated in patients with RET-altered
thyroid cancers with or without prior systemic therapy. Earlier
this year, the FDA granted accelerated approval to GAVRETO for the
treatment of adults with metastatic RET fusion-positive non-small
cell lung cancer (NSCLC) as detected by an FDA approved test.
"With this approval, Blueprint Medicines has achieved four
marketing authorizations this year across our lead programs, making
real our vision to bring transformative precision therapies to
patients globally," said Jeff
Albers, Chief Executive Officer of Blueprint Medicines.
"Today's approval also builds further momentum toward bringing
GAVRETO to a wide range of patients with RET-altered cancers. Now,
as we work with our partner Genentech to rapidly deliver GAVRETO to
patients with RET-altered non-small cell lung cancer and thyroid
cancers, we continue to explore the potential of GAVRETO to address
additional tumor types and treatment settings."
"Traditionally, we have treated patients with RET-altered
thyroid cancers with multi-kinase inhibitors, non-selective
therapies with modest efficacy and clinically significant side
effects. The FDA approval of pralsetinib (GAVRETO), a once-daily
RET-targeted therapy, advances the standard of care for these
patients," said Mimi Hu, M.D.,
professor in the Department of Endocrine Neoplasia and Hormonal
Disorders at The University of Texas MD
Anderson Cancer Center, and an investigator on the ARROW trial. "As
a clinical researcher with a focus on thyroid cancer, I am
encouraged by the safety profile and durable responses shown by
GAVRETO in RET-altered thyroid cancers in both treatment-naïve and
previously treated patients."
This approval is based on efficacy and safety results from the
ARROW trial.1 In 55 patients with RET-mutant MTC
previously treated with cabozantinib or vandetanib, the overall
response rate (ORR) was 60 percent (95% CI: 46%, 73%), and the
median duration of response (DOR) was not reached (95% CI: 15.1
months, not estimable). In 29 cabozantinib and vandetanib-naïve
patients with RET-mutant MTC who were not candidates for standard
systemic therapy per the study protocol, the ORR was 66 percent
(95% CI: 46%, 82%), and the median DOR was not reached (95% CI: not
estimable, not estimable). In addition, the ORR was 89 percent (95%
CI: 52%, 100%) in nine patients with RET fusion-positive thyroid
cancer, and the median DOR was not reached (95% CI: not estimable,
not estimable). In ARROW trial patients across RET-altered tumor
types, the most common adverse reactions (≥25%) were constipation,
hypertension, fatigue, musculoskeletal pain and diarrhea.
The continued approval of GAVRETO for advanced or metastatic
RET-altered thyroid cancers may be contingent upon verification and
description of clinical benefit in confirmatory trials. The FDA
approved these additional indications for GAVRETO under its
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.
"The FDA approval of GAVRETO has the potential to address
important medical needs for patients with RET-altered thyroid
cancers, and reflects a shift in care toward precision medicines
designed to target the underlying driver of disease," said
Gary Bloom, executive director of
ThyCa: Thyroid Cancer Survivors' Association (www.thyca.org). "We
are excited that the emergence of targeted therapies like GAVRETO,
combined with the expanded use of biomarker testing, may
dramatically improve treatment for the RET-altered thyroid cancer
community. At ThyCa, we are committed to advancing awareness of
these promising areas of clinical research, educating our members
on the importance of biomarker testing and offering support for
those impacted by the disease."
Biomarker testing for RET enables clinicians to identify
patients who are candidates for treatment with GAVRETO. RET
alterations can be identified with available biomarker tests,
including next-generation sequencing with tumor tissue or liquid
biopsies.
Blueprint Medicines is dedicated to helping patients access
GAVRETO and delivering support throughout their treatment journey.
As part of this commitment, Blueprint Medicines is providing
YourBlueprint™, a patient support program that offers access and
affordability solutions for individuals receiving GAVRETO. 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
GAVRETO can fill out an enrollment form at
YourBlueprint.com/HCP to help patients access the support
services.
About GAVRETO (pralsetinib)
GAVRETO (pralsetinib) is a once-daily oral targeted therapy
approved by the FDA for the treatment of three indications: adult
patients with metastatic RET fusion-positive NSCLC as detected by
an FDA approved test, adult and pediatric patients 12 years of age
and older with advanced or metastatic RET-mutant MTC who require
systemic therapy, and adults and pediatric patients 12 years of age
and older with advanced or metastatic RET fusion-positive thyroid
cancer who require systemic therapy and who are radioactive
iodine-refractory (if radioactive iodine is appropriate).
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.
GAVRETO is designed to selectively and potently target oncogenic
RET alterations, including secondary RET mutations predicted to
drive resistance to treatment. 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.
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 European Medicines
Agency validated a marketing authorization application for GAVRETO
for the treatment of RET fusion-positive NSCLC. The FDA 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, which encompasses Mainland China, Hong Kong, Macau and Taiwan.
Enrollment is ongoing in the Phase 1/2 ARROW trial, including
for patients with various RET fusion-positive solid tumors, and in
the Phase 3 AcceleRET Lung trial for treatment-naïve patients with
RET fusion-positive NSCLC. For more information about GAVRETO
clinical trials, visit www.clinicaltrials.gov or
www.blueprintclinicaltrials.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.
Important Safety Information
Interstitial Lung Disease (ILD)/Pneumonitis occurred
in 10% of patients who received GAVRETO, including 2.7% with Grade
3/4, and 0.5% with fatal reactions. Monitor for pulmonary symptoms
indicative of ILD/pneumonitis. Withhold GAVRETO and promptly
investigate for ILD in any patient who presents with acute or
worsening of respiratory symptoms (e.g., dyspnea, cough, and
fever). Withhold, reduce dose or permanently discontinue GAVRETO
based on severity of confirmed ILD.
Hypertension occurred in 29% of patients, including
Grade 3 hypertension in 14% of patients. Overall, 7% had their dose
interrupted and 3.2% had their dose reduced for hypertension.
Treatment-emergent hypertension was most commonly managed with
anti-hypertension medications. Do not initiate GAVRETO in patients
with uncontrolled hypertension. Optimize blood pressure prior to
initiating GAVRETO. Monitor blood pressure after 1 week, at least
monthly thereafter and as clinically indicated. Initiate or adjust
anti-hypertensive therapy as appropriate. Withhold, reduce dose, or
permanently discontinue GAVRETO based on the severity.
Hepatotoxicity: Serious hepatic adverse reactions
occurred in 2.1% of patients treated with GAVRETO. Increased
aspartate aminotransferase (AST) occurred in 69% of patients,
including Grade 3/4 in 5% and increased alanine aminotransferase
(ALT) occurred in 46% of patients, including Grade 3/4 in 6%. The
median time to first onset for increased AST was 15 days (range: 5
days to 1.5 years) and increased ALT was 22 days (range: 7 days to
1.7 years). Monitor AST and ALT prior to initiating GAVRETO, every
2 weeks during the first 3 months, then monthly thereafter and as
clinically indicated. Withhold, reduce dose or permanently
discontinue GAVRETO based on severity.
Grade ≥ 3 hemorrhagic events occurred in 2.5% of patients
treated with GAVRETO including one patient with a fatal hemorrhagic
event. Permanently discontinue GAVRETO in patients with severe or
life-threatening hemorrhage.
Tumor Lysis Syndrome (TLS): Cases of TLS have been
reported in patients with medullary thyroid carcinoma receiving
GAVRETO. Patients may be at risk of TLS if they have rapidly
growing tumors, a high tumor burden, renal dysfunction, or
dehydration. Closely monitor patients at risk, consider appropriate
prophylaxis including hydration, and treat as clinically
indicated.
Impaired wound healing can occur in patients who
receive drugs that inhibit the vascular endothelial growth factor
(VEGF) signaling pathway. Therefore, GAVRETO has the potential to
adversely affect wound healing. Withhold GAVRETO for at least 5
days prior to elective surgery. Do not administer for at least 2
weeks following major surgery and until adequate wound healing. The
safety of resumption of GAVRETO after resolution of wound healing
complications has not been established.
Based on findings from animal studies and its mechanism of
action, GAVRETO can cause fetal harm when administered to a
pregnant woman. Advise pregnant women of the potential risk to a
fetus. Advise females of reproductive potential to use effective
non-hormonal contraception during treatment with GAVRETO and for 2
weeks after the final dose. Advise males with female partners of
reproductive potential to use effective contraception during
treatment with GAVRETO and for 1 week after the final dose. Advise
women not to breastfeed during treatment with GAVRETO and for 1
week after the final dose.
Common adverse reactions (≥25%) were constipation,
hypertension, fatigue, musculoskeletal pain and diarrhea. Common
Grade 3/4 laboratory abnormalities (≥2%) were decreased
lymphocytes, decreased neutrophils, decreased hemoglobin, decreased
phosphate, decreased calcium (corrected), decreased sodium,
increased AST, increased ALT, decreased platelets and increased
alkaline phosphatase.
Avoid coadministration of GAVRETO with strong CYP3A
inhibitors or combined P-gp and strong CYP3A inhibitors. If
coadministration cannot be avoided, reduce the GAVRETO dose. Avoid
coadministration of GAVRETO with strong CYP3A inducers. If
coadministration cannot be avoided, increase the GAVRETO dose.
Please click here to see the full Prescribing Information for
GAVRETO.
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 approved precision therapies and are
currently advancing multiple investigational medicines in clinical
and pre-clinical development, along with a number of earlier-stage
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 FDA
approval of GAVRETO and the implications of such approval for
patients, caregivers and healthcare professionals; expectations
regarding patients' ability to rapidly access treatment with
GAVRETO; Blueprint Medicines' plans and ability to provide robust
support services for patients prescribed GAVRETO through
YourBlueprint; the potential benefits of Blueprint Medicines'
current and future approved drugs or drug candidates in treating
patients, including expectations regarding the potential of GAVRETO
to address additional tumor types and treatment settings; 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
continuing to establish and maintain 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® (avapritinib)
and GAVRETO or obtain marketing approval for AYVAKIT/AYVAKYT 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 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; and the success of Blueprint Medicines'
current and future collaborations, 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 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 GAVRETO™ (pralsetinib) Prescribing Information
(U.S.). Blueprint Medicines Corporation, Cambridge, Massachusetts, USA; December
2020.
Trademarks
Blueprint Medicines, AYVAKIT/AYVAKYT, GAVRETO, YourBlueprint and
associated logos are trademarks of Blueprint Medicines
Corporation.
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