BOULDER, Colo. , July 13, 2018 /PRNewswire/ -- Array
BioPharma Inc. (NASDAQ: ARRY) today announced that the National Comprehensive Cancer Network (NCCN) has updated the Clinical
Practice Guidelines in Oncology for Melanoma to include BRAFTOVI™ in combination with MEKTOVI® as a
Category 1 first-line and second-line treatment option for patients with BRAF V600E
or BRAF V600K-mutant metastatic or unresectable melanoma.
The U.S. Food and Drug Administration (FDA) approved BRAFTOVI in combination with MEKTOVI on June
27, 2018 for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E
or BRAF V600K mutation, as detected by an FDA-approved test based on
data from the pivotal 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 [hazard ratio (HR) (0.54), (95% CI 0.41-0.71),
p<0.0001]. In the trial, only 5% of patients who received BRAFTOVI + MEKTOVI discontinued treatment due to adverse reactions.
BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma.
"We greatly appreciate the NCCN's rapid evaluation and recommendation for BRAFTOVI + MEKTOVI as a Category
1 treatment option for patients with advanced BRAF-mutant melanoma," said Ron Squarer, Chief Executive
Officer. "These products represent a new standard of care for patients with this deadly type of skin cancer."
A Category 1 recommendation indicates that, based upon high-level evidence, there is uniform NCCN consensus that the
intervention is appropriate.
In June 2018, Array also announced updated results from the COLUMBUS trial which demonstrated that the combination
encorafenib and binimetinib reduced the risk of death compared to treatment with vemurafenib [HR (0.61), (95% CI 0.47-0.79, p
<0.0001] in the planned analysis of overall survival (OS). 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.
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 BRAF V600E or BRAF V600K 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 BRAFmutation-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 capsules in combination with MEKTOVI®
tablets for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or
BRAF V600K 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 July 13, 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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