BOULDER, Colo., June 27, 2018 /PRNewswire/ -- Array
BioPharma Inc. (Nasdaq: ARRY) today announced that the U.S. Food
and Drug Administration (FDA) has approved
BRAFTOVI™ capsules in combination with
MEKTOVI® tablets for the treatment of patients with
unresectable or metastatic melanoma with a
BRAFV600E or BRAFV600K
mutation, as detected by an FDA-approved test. BRAFTOVI is not
indicated for the treatment of patients with wild-type
BRAF melanoma.
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"We are thrilled with the approval of BRAFTOVI + MEKTOVI, which
help fill a critical unmet need for patients with advanced
BRAF-mutant melanoma, a serious and deadly type of skin
cancer," said Ron Squarer, Chief Executive Officer, Array
BioPharma. "As presented at ASCO, BRAFTOVI + MEKTOVI is the first
targeted treatment to demonstrate over 30 months median overall
survival in a Phase 3 trial. These products represent a new
standard of care for BRAF-mutant melanoma patients and we
sincerely thank the patients and dedicated researchers who
participated in our clinical program."
BRAFTOVI + MEKTOVI are now available to order through select
specialty pharmacies in the U.S. market.
"Despite recent advances, there remains a significant unmet need
for treatments that are both effective and well-tolerated for
patients with BRAF-mutant melanoma," said Keith T. Flaherty, M.D., Director of the Termeer
Center for Targeted Therapy, Massachusetts General Hospital Cancer
Center and Professor of Medicine, Harvard
Medical School. "Now, physicians and patients have the
option to consider treatment with BRAFTOVI + MEKTOVI, which has
been shown to delay disease progression, improve overall survival
and is generally well-tolerated."
"Nearly half of patients diagnosed with metastatic melanoma test
positive for the BRAF mutation," said Valerie Guild, Co-Founder and President of the
AIM at Melanoma Foundation. "Today's approval is welcome news for
the melanoma community as it arms BRAF-mutant late-stage
melanoma patients with an important new targeted treatment in their
fight against this devastating disease."
The approval of BRAFTOVI + MEKTOVI is based on results from the
Phase 3 COLUMBUS trial, which demonstrated the combination doubled
median progression-free survival (mPFS) compared to vemurafenib,
alone (14.9 months versus 7.3 months, respectively [HR (0.54), (95%
CI 0.41-0.71), p<0.0001]). Only 5% of patients who received
BRAFTOVI + MEKTOVI discontinued treatment due to adverse
reactions.
The most common adverse reactions (≥25%) in patients receiving
BRAFTOVI + MEKTOVI were fatigue, nausea, diarrhea, vomiting,
abdominal pain, and arthralgia.
As announced in February 2018, BRAFTOVI + MEKTOVI reduced the
risk of death compared to treatment with vemurafenib 960 mg daily
[hazard ratio (HR) of 0.61, [95% CI 0.47, 0.79, p <0.001] in the
planned analysis of overall survival (OS) from the COLUMBUS trial.
Median OS was 33.6 months for patients treated with the
combination, compared to 16.9 months for patients treated with
vemurafenib as a monotherapy. These positive results add to the
growing body of clinical evidence supporting the BRAF/MEK inhibitor
combination therapy and Array and its partners are working to
formally submit these results with global regulatory
authorities.
Array BioPharma is committed to providing access and
reimbursement support to all patients. Array offers a $0 copay for eligible, commercially-insured
patients. For more information about treatment of BRAFTOVI in
combination with MEKTOVI, visit www.braftovimektovi.com.
The full prescribing information for BRAFTOVI can be found
here:
http://www.arraybiopharma.com/documents/Braftovi_Prescribing_information.pdf
The full prescribing information for MEKTOVI can be found
here:
http://www.arraybiopharma.com/documents/Mektovi_Prescribing_information.pdf
About BRAF-mutant Metastatic Melanoma
Melanoma
develops when unrepaired DNA damage to skin cells triggers
mutations that may lead them to multiply and form malignant tumors.
Metastatic melanoma is the most serious and life-threatening type
of skin cancer and is associated with low survival rates. [1, 2]
There are a variety of gene mutations that can lead to metastatic
melanoma. The most common genetic mutation in metastatic melanoma
is BRAF. There are about 200,000 new cases of melanoma
diagnosed worldwide each year, approximately half of which
have BRAF mutations, a key target in the treatment
of metastatic melanoma. [1, 3, 4, 5]
About BRAFTOVI + MEKTOVI
BRAFTOVI is an oral small
molecule BRAF kinase inhibitor and MEKTOVI is an oral small
molecule MEK inhibitor which target key enzymes in the MAPK
signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of
proteins in this pathway has been shown to occur in many cancers
including melanoma, colorectal cancer, non-small cell lung cancer,
thyroid and others. In the U.S., BRAFTOVI + MEKTOVI are approved
for the treatment of unresectable or metastatic melanoma with a
BRAFV600E or BRAFV600K
mutation, as detected by an FDA-approved test. BRAFTOVI is not
indicated for treatment of patients with wild-type BRAF
melanoma.
Array has exclusive rights to BRAFTOVI and MEKTOVI in the U.S.
and Canada. Array has granted Ono
Pharmaceutical exclusive rights to commercialize both products in
Japan and South Korea and Pierre
Fabre exclusive rights to commercialize both products in all
other countries, including Europe,
Asia and Latin America.
BRAFTOVI + MEKTOVI are not approved outside of the U.S. The
European Medicines Agency (EMA), as well as the Swiss Medicines
Agency (Swissmedic) and the Australian Therapeutic Goods
Administration (TGA), are currently reviewing the Marketing
Authorization Applications submitted by Pierre Fabre, and Japan's Pharmaceuticals and Medical Devices
Agency has accepted the Manufacturing and Marketing Approval
applications submitted by Ono Pharmaceutical Co, Ltd.
About COLUMBUS
The COLUMBUS trial (NCT01909453) is a
two-part, international, randomized, open label Phase 3 trial
evaluating the efficacy and safety of BRAFTOVI (encorafenib) in
combination with MEKTOVI (binimetinib) compared to vemurafenib and
encorafenib monotherapy in 921 patients with locally advanced,
unresectable or metastatic melanoma with BRAFV600
mutation. All secondary efficacy analyses, including overall
survival, are descriptive in nature. Over 200 sites across
North America, Europe, South
America, Africa,
Asia and Australia participated in the trial.
Indications and Usage
BRAFTOVI™ (encorafenib) and
MEKTOVI® (binimetinib) are kinase
inhibitors indicated for use in combination for the treatment
of patients with unresectable or metastatic melanoma with a
BRAFV600E or BRAFV600K
mutation, as detected by an FDA-approved test.
Limitations of Use: BRAFTOVI is not indicated for the treatment
of patients with wild-type BRAF melanoma.
BRAFTOVI + MEKTOVI Important Safety Information
The information below applies to the safety of the combination
of BRAFTOVI and MEKTOVI unless otherwise noted.
Warnings and Precautions
New Primary Malignancies: New primary malignancies,
cutaneous and non-cutaneous malignancies can occur. In the COLUMBUS
trial, cutaneous squamous cell carcinoma, including
keratoacanthoma, occurred in 2.6% and basal cell carcinoma occurred
in 1.6% of patients. Perform dermatologic evaluations prior to
initiating treatment, every 2 months during treatment, and for up
to 6 months following discontinuation of treatment. Discontinue
BRAFTOVI for RAS mutation-positive non-cutaneous
malignancies.
Tumor Promotion in BRAF Wild-Type Tumors: Confirm
evidence of BRAFV600E or
BRAFV600K mutation prior to initiating
BRAFTOVI.
Cardiomyopathy: In the COLUMBUS trial, cardiomyopathy
occurred in 7% and Grade 3 left ventricular dysfunction occurred in
1.6% of patients. Cardiomyopathy resolved in 87% of patients.
Assess left ventricular ejection fraction by echocardiogram or MUGA
scan prior to initiating treatment, 1 month after initiating
treatment, and then every 2 to 3 months during treatment. The
safety has not been established in patients with a baseline
ejection fraction that is either below 50% or below the
institutional lower limit of normal.
Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE
occurred in 6% of patients, including 3.1% of patients who
developed pulmonary embolism.
Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in
19% of patients and ≥Grade 3 hemorrhage occurred in 3.2% of
patients. Fatal intracranial hemorrhage in the setting of new or
progressive brain metastases occurred in 1.6% of patients.
Ocular Toxicities: In the COLUMBUS trial, serous
retinopathy occurred in 20% of patients; 8% were retinal detachment
and 6% were macular edema. Symptomatic serous retinopathy occurred
in 8% of patients with no cases of blindness. In patients with
BRAF mutation-positive melanoma across multiple clinical
trials, 0.1% of patients experienced retinal vein occlusion (RVO).
Permanently discontinue MEKTOVI in patients with documented RVO. In
COLUMBUS, uveitis, including iritis and iridocyclitis, was reported
in 4% of patients. Assess for visual symptoms at each visit.
Perform ophthalmic evaluation at regular intervals and for any
visual disturbances.
Interstitial Lung Disease (ILD): ILD, including
pneumonitis, occurred in 0.3% of patients with BRAF
mutation-positive melanoma across multiple clinical trials. Assess
new or progressive unexplained pulmonary symptoms or findings for
possible ILD.
Hepatotoxicity: In the COLUMBUS trial, the incidence of
Grade 3 or 4 increases in liver function laboratory tests was 6%
for alanine aminotransferase (ALT) and 2.6% for aspartate
aminotransferase (AST). Monitor liver laboratory tests before and
during treatment and as clinically indicated.
Rhabdomyolysis: In the COLUMBUS trial, elevation of
laboratory values of serum creatine phosphokinase (CPK) occurred in
58% of patients. Rhabdomyolysis was reported in 0.1% of patients
with BRAF mutation-positive melanoma across multiple
clinical trials. Monitor CPK periodically and as clinically
indicated.
QTc Prolongation: In the COLUMBUS trial, an
increase in QTcF to >500 ms was measured in 0.5% (1/192) of
patients. Monitor patients who already have or who are at
significant risk of developing QTc prolongation. Correct
hypokalemia and hypomagnesemia prior to and during BRAFTOVI
administration. Withhold, reduce dose, or permanently discontinue
for QTc >500 ms.
Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause
fetal harm when administered to pregnant women. Nonhormonal
contraceptives should be used during treatment and for at least 30
days after the final dose for patients taking BRAFTOVI +
MEKTOVI.
Adverse Reactions
The most common adverse reactions
(≥20%, all Grades, in the COLUMBUS trial) were: fatigue, nausea,
diarrhea, vomiting, abdominal pain, arthralgia, myopathy,
hyperkeratosis, rash, headache, constipation, visual impairment,
serous retinopathy.
In the COLUMBUS Trial, the most common laboratory abnormalities
(≥20%, all Grades) included: increased creatinine, increased CPK,
increased gamma glutamyl transferase, anemia, increased ALT,
hyperglycemia, increased AST, and increased alkaline
phosphatase.
Drug interactions
Avoid concomitant use of strong or
moderate CYP3A4 inhibitors or inducers and sensitive CYP3A4
substrates with BRAFTOVI. Modify BRAFTOVI dose if concomitant
use of strong or moderate CYP3A4 inhibitors cannot be avoided.
Please see full Prescribing Information for BRAFTOVI and full
Prescribing Information for MEKTOVI for additional
information. You may report side effects to the FDA at
(800) FDA-1088 or www.fda.gov/medwatch. You may also report side
effects to Array at 1-844-Rx-Array (1-844-792-7729).
About Array BioPharma
Array BioPharma Inc. is a
fully-integrated, biopharmaceutical company focused on the
discovery, development and commercialization of safe and effective
targeted small molecule drugs to treat patients afflicted with
cancer and other conditions. Array markets in the United States BRAFTOVITM
(encorafenib) capsules in combination with MEKTOVI®
(binimetinib) tablets for the treatment of patients with
unresectable or metastatic melanoma with a
BRAFV600E or BRAFV600K
mutation. Array's lead clinical programs, encorafenib and
binimetinib, are being investigated in over 30 clinical trials
across a number of solid tumor indications, including a Phase 3
trial in BRAF-mutant colorectal cancer. Array's pipeline
includes several additional advanced programs including selumetinib
(partnered with AstraZeneca), larotrectinib (partnered with Loxo
Oncology), ipatasertib (partnered with Genentech), tucatinib
(partnered with Seattle Genetics) and ARRY-797 (being developed by
Yarra Therapeutics, a wholly-owned subsidiary of Array), all of
which are currently in registration trials. Ganovo®
(danoprevir, partnered with Roche) was recently approved in
China for the treatment of viral
hepatitis C. For more information on Array, please visit
www.arraybiopharma.com or follow @arraybiopharma on Twitter and
LinkedIn.
References
1 Melanoma Skin
Cancer. American Cancer Society. Available
at: https://www.cancer.org/cancer/melanoma-skin-cancer.html.
Accessed January 2018.
2 A Snapshot of Melanoma. National Cancer
Institute. Available
at: https://seer.cancer.gov/statfacts/html/melan.html.
Accessed January 2018.
3 Globocan 2012: Estimated Cancer Incidence,
Mortality and Prevalence Worldwide in
2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
Accessed January 2018.
4 Klein O, et al. Eur J Cancer,
2013.
5 American Cancer Society. What Causes Melanoma Skin
Cancer? 2016.
https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/what-causes.html.
Accessed April 11, 2018.
6 BRAFTOVI™ (encorafenib) Prescribing Information. Array
BioPharma Inc., June 2018
7 MEKTOVI® (binimetinib) Prescribing
Information. Array BioPharma Inc., June
2018
Array BioPharma Forward-Looking Statement
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including, among others, statements about the future development
plans of encorafenib and binimetinib; expectations that events will
occur that will create greater value for Array; and the potential
for the results of current and future clinical trials to support
regulatory approval or the marketing success of encorafenib and
binimetinib. Because these statements reflect our current
expectations concerning future events and involve significant risks
and uncertainties, our actual results could differ materially from
those anticipated in these forward-looking statements as a result
of many factors. These factors include, but are not limited to, the
potential that the FDA, EMA or other regulatory agencies determine
results from clinical trials are not sufficient to support
registration or marketing approval of encorafenib and binimetinib;
our ability to effectively and timely conduct clinical trials in
light of increasing costs and difficulties in locating appropriate
trial sites and in enrolling patients who meet the criteria for
certain clinical trials; risks associated with our dependence on
third-party service providers to successfully conduct clinical
trials and to manufacture drug substance and product within and
outside the U.S.; our ability to grow and successfully develop
commercialization capabilities; our ability to achieve and maintain
profitability and maintain sufficient cash resources; and our
ability to attract and retain experienced scientists and
management. Additional information concerning these and other risk
factors can be found in our most recent annual report filed on Form
10-K, in our quarterly reports filed on Form 10-Q, and in other
reports filed by Array with the Securities and Exchange Commission.
We are providing this information as of June
27, 2018. We undertake no duty to update any forward-looking
statements to reflect the occurrence of events or circumstances
after the date of such statements or of anticipated or
unanticipated events that alter any assumptions underlying such
statements.
BRAFTOVI™ is a trademark of Array BioPharma Inc.
MEKTOVI® is a registered trademark of Array BioPharma
Inc. in the United States and
various other countries.
CONTACTS:
Investor Relations
Array BioPharma
Andrea N.
Flynn, Ph.D.
Senior Director, Investor Relations & Corporate
Communications
(303) 381-6600
ir@arraybiopharma.com
Media
Y&R PR
Erika Hackmann,
Media Relations
(917) 538-3375
erika.hackmann@yr.com
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SOURCE Array BioPharma Inc.