- FDA Grants Priority Review, Assigns Action Date of August 11,
2015 -
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Feb. 19, 2015--
Exelixis, Inc. (NASDAQ:EXEL) announced today that the U.S. Food and Drug
Administration (FDA) has accepted for review Genentech’s New Drug
Application (NDA) for cobimetinib in combination with vemurafenib for
patients with unresectable or metastatic melanoma harboring a BRAF V600
mutation. Cobimetinib is a specific MEK inhibitor that was discovered by
Exelixis and is now the subject of a worldwide co-development agreement
between Exelixis and Genentech, a member of the Roche Group.
FDA has granted Priority Review to the NDA and assigned a Prescription
Drug User Fee Act (PDUFA) action date of August 11, 2015. A Priority
Review designation is granted to medicines that the FDA determines have
the potential to provide significant improvements in the treatment,
prevention or diagnosis of a disease.
“The FDA’s acceptance of the cobimetinib NDA brings us one step closer
to a potential new treatment option for patients with advanced BRAF V600
mutation-positive melanoma, a form of the disease for which new
approaches are needed,” said Michael M. Morrissey, Ph.D., president and
chief executive officer of Exelixis. “We applaud Genentech on this
regulatory progress, and we look forward to working with them, as well
as with Roche, to commercialize and co-promote the combination in the
event that it is approved.”
The NDA is based on data from coBRIM, a phase 3 pivotal trial conducted
by Genentech. Roche also submitted a Marketing Authorization Application
(MAA) to the European Medicines Agency for the combination of
cobimetinib and vemurafenib in 2014.
About the coBRIM Study
The coBRIM trial is an international, randomized, double-blind,
placebo-controlled Phase III study evaluating the safety and efficacy of
60 mg once daily of cobimetinib in combination with 960 mg twice daily
of vemurafenib, compared to 960 mg twice daily of vemurafenib alone. In
the study, 495 patients with BRAF V600 mutation-positive unresectable
locally advanced or metastatic melanoma (detected by the cobas® 4800
BRAF Mutation Test) and previously untreated for advanced disease, were
randomized to receive vemurafenib every day on a 28-day cycle plus
either cobimetinib or placebo for days 1-21. Treatment was continued
until disease progression, unacceptable toxicity or withdrawal of
consent. At the time of the primary analysis, median follow up was 7.4
months for the combination arm and 7.2 months for the control arm.
As presented during the Presidential Symposium at the European Society
for Medical Oncology 2014 Congress, coBRIM met its primary endpoint,
demonstrating a statistically significant increase in
investigator-determined progression-free survival (PFS). The median PFS
was 9.9 months for the combination of cobimetinib and vemurafenib versus
6.2 months for vemurafenib alone (hazard ratio [HR] = 0.51, 95 percent
CI 0.39-0.68; p < 0.0001). The safety profile of the combination was
consistent with that observed in a previous study of the combination.
The most common Grade 3 or higher adverse events in the combination arm
included liver laboratory abnormalities, elevated creatine phosphokinase
and diarrhea. The most common adverse events seen in the combination arm
included diarrhea, nausea, rash, photosensitivity and laboratory value
abnormalities.
About the Cobimetinib Development Collaboration
Exelixis discovered cobimetinib internally and advanced the compound to
investigational new drug (IND) status. In late 2006, Exelixis entered
into a worldwide co-development agreement with Genentech, under which
Exelixis received initial upfront and milestone payments in connection
with signing the agreement and submitting the IND. Exelixis was
responsible for development of cobimetinib through the determination of
the maximum tolerated dose in phase 1, at which point Genentech
exercised its option to further develop the compound.
In November 2013, Exelixis exercised its option to co-promote
cobimetinib, if approved, in the United States. Exelixis is entitled to
an initial equal share of U.S. profits and losses, which will decrease
as sales increase, and will share equally in the U.S. marketing and
commercialization costs. Exelixis is eligible to receive royalties on
any sales of the product outside the United States.
About the Cobimetinib and Vemurafenib Combination
Cobimetinib is a selective inhibitor that blocks the activity of MEK, a
protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK
pathway) that promotes cell division and survival. This pathway is
frequently activated in human cancers including melanoma, where mutation
of one of its components (BRAF) causes abnormal activation in about 50%
of tumors. Tumors with BRAF mutations may develop resistance and
subsequently progress after treatment with a BRAF inhibitor. In
preclinical melanoma models, co-treatment with vemurafenib and the MEK
inhibitor cobimetinib may delay the emergence of resistant tumors. In
addition to the combination with vemurafenib in melanoma, cobimetinib is
also being investigated in combination with several investigational
medicines, including an immunotherapy, in several tumor types, including
non-small cell lung cancer, colorectal cancer, triple-negative breast
cancer and melanoma.
About Melanoma and its BRAF V600 Mutation-Positive Form
Melanoma is the less common, but more serious category of skin cancer
that starts in the skin’s pigment producing cells known as melanocytes.
According to the American Cancer Society, approximately five percent of
skin cancer diagnoses are melanoma, but melanoma accounts for a large
majority of skin cancer deaths. In recent years, there have been
significant advances in treatment for metastatic melanoma and people
with the disease have more options. However, it continues to be a
serious health issue with a high unmet need and a steadily increasing
incidence over the past 30 years. It is projected that approximately
half of all melanomas, and eight percent of solid tumors, contain a
mutation of the BRAF protein. BRAF is a key component of the
RAS-RAF-MEK-ERK pathway involved in normal cell growth and survival.
However, mutations that keep the BRAF protein in an active state may
cause excessive signaling in the pathway, leading to uncontrolled cell
growth and survival. The BRAF V600 mutation-positive form of melanoma is
associated with high-risk characteristics of the disease, including
early onset, the absence of chronic skin damage, and decreased survival.
About Exelixis
Exelixis, Inc. is a biopharmaceutical company committed to developing
small molecule therapies for the treatment of cancer. Exelixis is
focusing its development and commercialization efforts primarily on
COMETRIQ® (cabozantinib), its wholly-owned inhibitor of
multiple receptor tyrosine kinases. Another Exelixis-discovered
compound, cobimetinib, a highly selective inhibitor of MEK, is being
evaluated by Roche and Genentech (a member of the Roche Group) in a
broad development program under a collaboration with Exelixis. For more
information, please visit the company's web site at www.exelixis.com.
Forward-Looking Statements
This press release contains forward-looking statements, including,
without limitation, statements related to: potential regulatory approval
for cobimetinib and the timing thereof; Exelixis’ future U.S.
co-promotion efforts for cobimetinib in the United States; the plan of
Genentech and Exelixis to share U.S. profits and losses for cobimetinib
and U.S. marketing and commercialization costs for cobimetinib; and
Exelixis’ potential receipt of royalties on sales of cobimetinib
products outside the United States. Words such as “potential,” “brings,”
“progress,” “projected,” “if,” “entitled,” “will,” “eligible,” and
similar expressions are intended to identify forward-looking statements.
These forward-looking statements are based upon Exelixis’ (and its
partner Genentech’s) current plans, assumptions, beliefs, expectations,
estimates and projections. Forward-looking statements involve risks and
uncertainties. Exelixis’ actual results and the timing of events could
differ materially from those anticipated in the forward-looking
statements as a result of these risks and uncertainties, which include,
without limitation: risks related to: the clinical, therapeutic and
commercial value of cobimetinib; Exelixis’ dependence on its
relationship with Genentech/Roche with respect to cobimetinib and
Exelixis’ ability to maintain its rights under the collaboration; risks
and uncertainties related to regulatory review and approval processes
and Exelixis’ compliance with applicable legal and regulatory
requirements; market competition; changes in economic and business
conditions; and other factors discussed under the caption “Risk Factors”
in Exelixis’ quarterly report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) on November 4, 2014 and in Exelixis' other
filings with the SEC. The forward-looking statements made in this press
release speak only as of the date of this press release. Exelixis
expressly disclaims any duty, obligation or undertaking to release
publicly any updates or revisions to any forward-looking statements
contained herein to reflect any change in Exelixis’ expectations with
regard thereto or any change in events, conditions or circumstances on
which any such statements are based.
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
trademarks.
Source: Exelixis, Inc.
Exelixis, Inc.
Susan Hubbard, 650-837-8194
Investor
Relations and
Corporate Communications
shubbard@exelixis.com
