- Updated results from coBRIM phase 3 pivotal
trial show median progression-free survival of one year for
patients with BRAF V600 mutation-positive advanced melanoma –
- Additional data from phase 1b BRIM7 study
showed 61 percent of patients who had not been previously treated
with a BRAF inhibitor were alive after two years -
- Cobimetinib for use in combination with
vemurafenib is the subject of pending U.S. and European regulatory
applications, with U.S. PDUFA date of August 11, 2015 -
Exelixis Inc. (NASDAQ:EXEL) today announced updated positive
results for cobimetinib, an Exelixis-discovered investigational
compound, in combination with vemurafenib for the treatment of
patients with previously untreated BRAF V600 mutation-positive
advanced melanoma. Updated data from coBRIM (Abstract #9006), the
phase 3 pivotal trial conducted by Exelixis’ collaborator
Genentech, a member of the Roche Group, showed the combination
helped patients with previously untreated BRAF V600
mutation-positive advanced melanoma live a median of one year (12.3
months) without disease progression or death, compared to 7.2
months with vemurafenib alone (hazard ratio [HR] = 0.58, 95%
confidence interval [CI] 0.46-0.72). Data from a second trial, the
phase 1b BRIM7 study (Abstract #9020), showed that treatment with
the combination resulted in a median overall survival of more than
two years (28.5 months) for patients without prior BRAF inhibitor
treatment. Both data sets will be presented at the 2015 Annual
Meeting of the American Society of Clinical Oncology (ASCO), which
is being held this week in Chicago, Illinois.
“The updated results for the combination of cobimetinib and
vemurafenib, including a median progression-free survival of one
year in patients with previously untreated BRAF V600
mutation-positive advanced melanoma, are encouraging,” said Michael
M. Morrissey, Ph.D., president and chief executive officer of
Exelixis. “The data underscore the potential for the combination to
become a meaningful new treatment option for patients with this
type of melanoma. We congratulate Genentech and Roche on two
well-run trials, and we look forward to working with them to bring
the combination to physicians and patients in the event of
potential regulatory approval later this year.”
The updated results from coBRIM also showed higher response
rates with cobimetinib and vemurafenib compared to vemurafenib
alone. Objective response rate, a secondary endpoint of the trial,
was 70% (16% compete response [CR], 54% partial response [PR]) with
the combination compared to 50% (11% CR, 40% PR) with vemurafenib
alone. The CR rate with the combination has increased from 10% to
16% with further follow-up as some patients who had an initial PR
achieved a CR after more than one year of treatment. The safety
profile of the combination was consistent with data previously
reported. The most common adverse events in the combination arm
include diarrhea, rash, nausea, fever, sun sensitivity, liver lab
abnormalities, elevated creatine phosphokinase (CPK, an enzyme
released by muscles) and vomiting.
Follow-up data from BRIM7, the phase 1b study that provided the
rationale for the coBRIM pivotal trial, demonstrated that the
combination of cobimetinib and vemurafenib resulted in a median
overall survival of 28.5 months, with 61% of BRAF inhibitor-naive
patients remaining alive after two years. The safety profile from
the BRIM7 trial was consistent with previous analyses, and the
incidence of serous retinopathy, cardiomyopathy and cutaneous
squamous cell carcinoma were similar to those previously
reported.
The coBRIM data will be presented in an oral session today by
Dr. James Larkin, FRCP, of The Royal Marsden Hospital, London, UK
(Abstract #9006, May 30, 3:15-3:27 pm CDT), while the BRIM7 data
will be presented in a poster session by Dr. Anna Pavlick, New York
University Medical Center (Abstract #9020, June 1, 1:15-4:45 pm
CDT).
The cobimetinib New Drug Application for BRAF V600
mutation-positive advanced melanoma was granted priority review by
the U.S. Food and Drug Administration (FDA) and a decision is
expected by August 11, 2015. The European Medicines Agency is
expected to make a decision on Roche’s marketing authorization
application for cobimetinib before the end of this year.
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. Investigator-assessed PFS is the primary endpoint.
Secondary endpoints include PFS by independent review committee,
overall response rate, overall survival, duration of response and
other safety, pharmacokinetic and quality of life measures.
The most common adverse events reported in patients taking
cobimetinib in combination with vemurafenib (≥ 20%) were diarrhea,
rash, nausea, fever, sun sensitivity, liver lab abnormalities,
elevated creatine phosphokinase (CPK, an enzyme released by
muscles) and vomiting. Serous retinopathy (collection of fluid
under the retina) was observed at a higher frequency in the
combination arm (26% vs. 3%) with most of these events either Grade
1 or 2, asymptomatic, and temporary in nature. Some adverse events,
including cutaneous squamous cell carcinomas and keratoacanthomas,
were reported less frequently in the combination arm.
About the BRIM7 Study
BRIM7 is a Phase 1b study of 129 patients evaluating the safety
and tolerability of cobimetinib in combination with vemurafenib in
people with BRAF V600 mutation-positive unresectable or metastatic
melanoma who had either not been previously treated with a BRAF
inhibitor or had shown disease progression following treatment with
a BRAF inhibitor. The primary endpoint of the BRIM7 study focused
on safety, tolerability, and the identification of an optimal dose.
The secondary outcome measures focused on efficacy. Patients in the
dose-escalation stage of the study received cobimetinib 60, 80 or
100 mg once daily given on a schedule of 14 days on/14 days off; 21
days on/7 days off; or continuously for 28 days, and vemurafenib
720 or 960 mg twice daily continuously. Following the
dose-escalation stage, two dose levels were selected for further
investigation: cobimetinib 60 mg once daily for 21 days on/7 days
off and vemurafenib (720 mg or 960 mg twice daily).
The most common adverse events were mild to moderate in
severity, and the overall frequency of adverse events with an
extended median follow-up of up to 21 months have remained
consistent without new safety signals.
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 collaboration 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 a BRAF inhibitor and a MEK inhibitor 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: the continued
development and clinical, therapeutic and commercial potential of
cobimetinib for use in combination with vemurafenib; future
potential regulatory approvals of cobimetinib; data presentations
for the coBRIM phase 3 pivotal trial and the phase 1b BRIM7 study;
Exelixis’ co-promotion efforts with Genentech in the event of
regulatory approval; the plan of Genentech
and Exelixis to share U.S. profits and losses for
cobimetinib and U.S. marketing and commercialization costs for
cobimetinib; Exelixis’ potential receipt of royalties on sales
of cobimetinib products outside the United States; and
projections and assumptions regarding melanoma. Words such as
“will,” “encouraging,” “potential,” “look forward,” “expected,”
“entitled,” “eligible,” “projected,” “may,” “committed,”
“focusing,” or other similar expressions, identify forward-looking
statements, but the absence of these words does not necessarily
mean that a statement is not forward-looking. In addition, any
statements that refer to expectations, projections or other
characterizations of future events or circumstances are
forward-looking statements. These forward-looking statements are
based upon Exelixis’ 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 potential failure of cobimetinib to demonstrate
safety and efficacy in clinical testing; the availability of data
at the expected times; 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; the general sufficiency of Exelixis’ capital and
other resources; 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 April 30, 2015 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20150530005027/en/
Investors Contact:Exelixis, Inc.Susan Hubbard,
650-837-8194Investor Relations and Corporate
Communicationsshubbard@exelixis.comorMedia Contact:For
Exelixis, Inc.Hal Mackins,
415-994-0040hal@torchcommunications.com
Exelixis (NASDAQ:EXEL)
Historical Stock Chart
From Mar 2024 to Apr 2024
Exelixis (NASDAQ:EXEL)
Historical Stock Chart
From Apr 2023 to Apr 2024