SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Sep. 29, 2012--
Exelixis, Inc. (NASDAQ:EXEL) today announced preliminary results from
BRIM7, an ongoing Phase Ib trial conducted by Roche and Genentech,
Exelixis' collaborator and a member of the Roche Group (SIX: RO, ROG;
OTCQX: RHHBY), of the BRAF inhibitor (BRAFi) vemurafenib in combination
with the MEK inhibitor GDC-0973 in patients with locally
advanced/unresectable or metastatic melanoma carrying a BRAFV600
mutation. Rene Gonzalez, M.D., Professor of Medicine and Dermatology and
Director of the Melanoma Research Clinics at the University of Colorado
Denver, and an investigator on the trial, presented the data today at
the European Society for Medical Oncology (ESMO) 2012 Annual Meeting
(Abstract #LBA28), which is taking place in Vienna, Austria. The results
of the study were also highlighted in an ESMO press briefing.
Roche has disclosed that it intends to evaluate the combination of
vemurafenib with GDC-0973 versus vemurafenib in a multicenter,
randomized, double-blind, placebo-controlled Phase III trial in
previously untreated patients with BRAFV600 mutation
positive, unresectable locally advanced or metastatic melanoma.
Study Design
The Phase Ib dose escalation study was designed to evaluate the safety
and tolerability of vemurafenib in combination with GDC-0973. The study
was not designed to measure efficacy. The dose escalation stage of the
trial comprised 10 dosing cohorts of 3-6 patients and evaluated three
different dosing schedules for GDC-0973. Cohorts that met the
protocol-specified criteria for safety were expanded to include up to 20
BRAFi-naïve and vemurafenib-progressing patients.
Study Results
As of July 6, 2012, 70 patients had been treated. The majority of
patients (74.3%) had Stage IV, M1c melanoma at the time of enrollment,
and 54.3% had disease progression following prior treatment with
vemurafenib. The median number of prior treatment cycles to date was
three. Six of the 10 dose escalation cohorts have met the
protocol-specified criteria for safety. One dose-limiting toxicity
(Grade 3 QT interval prolongation) was observed out of six patients in
the dose escalation stage receiving 960 mg of vemurafenib and 60 mg of
GDC-0973 on a 21/7 day schedule. Two cohorts receiving 60 mg of GDC-0973
on a 21/7 day schedule with vemurafenib at 720 mg and 960 mg were
selected for expansion.
The most common adverse events (AEs) attributed to either vemurafenib or
GDC-0973 in the 70 patients treated to date were: non-acneiform rash
(52.9%; 7.1% Grade 3 or 4), diarrhea (51.4%; 5.7%),
photosensitivity/sunburn (31.4%; 0%), fatigue (30.0%; 1.4%), and nausea
(28.6%; 1.4%). Selected AEs attributed to either vemurafenib or GDC-0973
were: creatinine phosphokinase elevation (20.0%; 4.3%), liver function
test elevation (20.0%; 4.3%), arthralgia (12.9%; 1.4%), serous
choreoretinopathy (4.3%; 0%), and cutaneous squamous cell carcinoma
(1.4%; 1.4%).
Temporary interruptions in vemurafenib, GDC-0973, or the combination of
both agents were reported in 24.3%, 21.4%, and 8.6% of patients,
respectively. One patient receiving the combination discontinued
vemurafenib permanently because of QT interval prolongation. No patients
receiving the combination of vemurafenib and GDC-0973 discontinued
treatment due to an adverse event.
All 24 BRAFi-naïve patients evaluable for tumor responses had a decrease
in tumor size from baseline, however, further follow-up is required to
determine the confirmed objective response rate.
About GDC-0973 (XL518)
GDC-0973 is a potent, highly selective inhibitor of MEK, a
serine/threonine kinase that is a component of the RAS/RAF/MEK/ERK
pathway. This pathway mediates signaling downstream of growth factor
receptors, and is prominently activated in a wide variety of human
tumors. In preclinical studies, oral dosing of GDC-0973 resulted in
potent and sustained inhibition of MEK in RAS or BRAF mutant tumor
models. GDC-0973 is being developed by Genentech, a member of the Roche
Group under a collaboration agreement with Exelixis.
About Collaboration
Exelixis discovered GDC-0973 (XL518) 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 for signing the agreement and submitting the IND. Exelixis was
responsible for development of GDC-0973 through the end of Phase I, at
which point Genentech exercised its option to further develop the
compound.
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.
Exelixis has the option to co-promote in the United States.
About Exelixis
Exelixis, Inc. is a biotechnology company committed to developing small
molecule therapies for the treatment of cancer. Exelixis is focusing its
proprietary resources and development efforts exclusively on
cabozantinib (formerly known as XL184), its most advanced product
candidate, in order to maximize the therapeutic and commercial potential
of this compound. Exelixis has also established a portfolio of other
novel compounds that it believes have the potential to address serious
unmet medical needs, many of which are being advanced by partners as
part of collaborations. For more information, please visit the company's
web site at www.exelixis.com.
Forward-Looking Statements
This press release contains forward-looking statements by Exelixis,
including, without limitation, statements related to: the continued
development and clinical and therapeutic potential of GDC-0973 (XL518);
the plan of Genentech and Exelixis to share U.S. profits and losses for
GDC-0973 (XL518) and U.S. marketing and commercialization costs for
GDC-0973 (XL518); Exelixis' potential receipt of royalties for GDC-0973
(XL518) products sales outside the United States; and Exelixis’ option
to co-promote in the United States. Words such as “will,” “intends,”
“entitled,” “share,” “option,” “designed,” “believes,” “potential,” and
similar expressions are intended to identify forward-looking statements.
These forward-looking statements are based upon Exelixis' current plans,
assumptions, beliefs and expectations. Forward-looking statements
involve risks and uncertainties. Exelixis' actual results and the timing
of events could differ materially from those anticipated in such
forward-looking statements as a result of these risks and uncertainties,
which include, without limitation: risks related to the potential
failure of GDC-0973 (XL518) to demonstrate safety and efficacy in
clinical testing; the therapeutic and commercial value of GDC-0973
(XL518); Exelixis' dependence on its relationship with Genentech/Roche
and Exelixis’ ability to maintain its rights under the collaboration;
the uncertainty of the FDA approval process; market competition; and
changes in economic and business conditions. These and other risk
factors are discussed under “Risk Factors” and elsewhere in Exelixis’
quarterly report on Form 10-Q for the quarter ended June 29, 2012, filed
with the Securities and Exchange Commission (SEC) on August 2, 2012, and
Exelixis’ other filings with the SEC. 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.
Source: Exelixis, Inc.
Exelixis, Inc.
Charles Butler, 650-837-7277
Vice President,
Investor Relations and Corporate Communications
cbutler@exelixis.com
