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
BRAFV600E or BRAFV600K-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 BRAFV600E or
BRAFV600K
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 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 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 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 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
View original content with
multimedia:http://www.prnewswire.com/news-releases/the-national-comprehensive-cancer-network-nccn-guidelines-recommend-braftovi-encorafenib-in-combination-with-mektovi-binimetinib-as-a-category-1-treatment-option-for-patients-with-advanced-braf-mutant-melanoma-300680562.html
SOURCE Array BioPharma Inc.