-- Exelixis will host conference call at 5:00 p.m. EST / 2:00 p.m.
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Nov. 29, 2012--
Exelixis, Inc. (NASDAQ: EXEL) today announced that the U.S. Food and
Drug Administration (FDA) has approved COMETRIQ™
(cabozantinib) for the treatment of progressive, metastatic medullary
thyroid cancer (MTC). COMETRIQ is an inhibitor of multiple receptor
tyrosine kinases involved in both normal cellular function and
pathologic processes such as oncogenesis, metastasis, tumor
angiogenesis, and maintenance of the tumor microenvironment. The
COMETRIQ label has boxed warnings concerning risk of perforations and
fistulas, and hemorrhage.
Exelixis completed its rolling New Drug Application (NDA) in May 2012,
and the FDA granted Priority Review Designation to the filing, assigning
a Prescription Drug User Fee Act (PDUFA) action date of November 29,
2012. The COMETRIQ approval is based on the results of EXAM, a
randomized phase 3 clinical trial conducted in 330 patients with
progressive, metastatic MTC, which met its primary efficacy endpoint of
improving progression-free survival (PFS).
“The approval of COMETRIQ is an important milestone for patients with
progressive, metastatic medullary thyroid cancer, their families, and
their physicians, as well as for Exelixis,” said Michael M. Morrissey,
Ph.D., president and chief executive officer of Exelixis. “We are
grateful to the many patients who participated in the clinical
development of COMETRIQ in MTC, and we are committed to making this
important new therapy available as quickly as possible.”
The recommended dose of COMETRIQ is 140 mg orally, once daily (one 80 mg
capsule and three 20 mg capsules). COMETRIQ should not be taken with
food, and patients are advised to not eat for at least 2 hours before
and at least 1 hour after taking COMETRIQ. Full prescribing information,
including Boxed Warning, is available at www.exelixis.com
“There has been little clinical progress in treating advanced MTC until
the introduction of targeted therapies, and it is gratifying to give
these patients a new treatment option that has been shown in clinical
trials to improve progression-free survival remarkably by nearly
three-fold,” said Steven I. Sherman, M.D., Naguib Samaan Distinguished
Professor in Endocrinology at M.D. Anderson Cancer Center and a senior
investigator in the phase 3 study. “The availability of a new
therapeutic approach that has the potential to improve patient care and
outcomes changes the MTC treatment landscape and provides patients and
physicians with a new way to manage the disease.”
COMETRIQ Conference Call and Webcast Information
Exelixis' management will discuss the company's plans to launch COMETRIQ
in MTC during a conference call beginning at 5:00 p.m. EST / 2:00 p.m.
PST today, Thursday, November 29, 2012. To listen to a live webcast of
the discussion, visit the Event Calendar page under Investors at www.exelixis.com
or access this page directly: http://www.media-server.com/m/p/o5e857m6.
An archived replay of the webcast will be available on the Event
Calendar page under Investors at www.exelixis.com
and via phone until 11:59 p.m. PST on December 29, 2012. Access numbers
for the phone replay are: 888-286-8010 (domestic) and 617-801-6888
(international); the passcode is 91510575.
COMETRIQ’s safety and efficacy was assessed in an international,
multi-center, randomized double-blinded controlled trial called EXAM of
330 patients with progressive, metastatic medullary thyroid carcinoma
(MTC). Patients were required to have evidence of actively progressive
disease within 14 months prior to study entry confirmed by an
Independent Radiology Review Committee (IRRC) masked to treatment
assignment (89%) or the treating physician (11%). Patients were
randomized (2:1) to receive COMETRIQ 140 mg (n = 219) or placebo (n =
111) orally, once daily until disease progression determined by the
treating physician or until intolerable toxicity. Randomization was
stratified by age (≤65 years vs. > 65 years) and prior use of a tyrosine
kinase inhibitor (TKI). No cross-over was allowed at the time of
progression. The main efficacy outcome measures of PFS, objective
response and response duration were based on IRRC-confirmed events using
the modified RECIST criteria.
A statistically significant prolongation in PFS was demonstrated among
COMETRIQ-treated patients compared to those receiving placebo [HR 0.28
(95% CI: 0.19, 0.40); p<0.0001], with median PFS times of 11.2 months
and 4.0 months in the COMETRIQ and placebo arms, respectively. Partial
responses were observed only among patients in the COMETRIQ arm (27% vs
0; p<0.0001). The median duration of objective responses was 14.7 months
(95% CI: 11.1, 19.3) for patients treated with COMETRIQ. There was no
statistically significant difference in overall survival between the
treatment arms at the planned interim analysis.
COMETRIQ Mechanism of Action
COMETRIQ (cabozantinib) inhibits the activity of tyrosine kinases
including RET, MET and VEGFR2. These receptor tyrosine kinases are
involved in both normal cellular function and in pathologic processes
such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of
the tumor microenvironment.
COMETRIQ™ Important Safety Information, including Boxed Warning
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
Serious and sometimes fatal gastrointestinal perforations and
fistulas occur in COMETRIQ-treated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated
COMETRIQ treatment results in an increase in thrombotic events, such
as heart attacks.
Wound complications have been reported with COMETRIQ.
COMETRIQ treatment results in an increase in hypertension.
Osteonecrosis of the jaw has been observed in COMETRIQ-treated
Palmar-Plantar Erythrodysesthesia (PPE) Syndrome occurs in patients
treated with COMETRIQ.
The kidneys can be adversely affected by COMETRIQ. Proteinuria and
nephrotic syndrome have been reported in patients receiving COMETRIQ.
Reversible Posterior Leukoencephalopathy Syndrome has been observed
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions
(≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia
syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue,
oral pain, hair color changes, dysgeusia, hypertension, abdominal pain,
and constipation. The most common laboratory abnormalities (≥25%) are
increased AST, increased ALT, lymphopenia, increased alkaline
phosphatase, hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Drug Interactions – COMETRIQ is a CYP3A4 substrate. Co-administration of
strong CYP3A4 inhibitors can increase cabozantinib exposure. Chronic
co-administration of strong CYP3A4 inducers can reduce cabozantinib
For full prescribing information, including Boxed Warning, please visit www.exelixis.com
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 its lead
product, COMETRIQ. 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.
This press release contains forward-looking statements, including,
without limitation, statements related to: the significance of the
referenced approval of COMETRIQ for patients, their families, physicians
and Exelixis; the clinical, therapeutic and commercial potential of
COMETRIQ; and Exelixis’ plans and expectations regarding the launch,
commercialization, distribution and availability of COMETRIQ. Words such
as “milestone,” “committed,” “available,” “new,” “quickly as possible,”
“new,” “option,” “shown,” “potential,” “provides,” 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: the risk that unanticipated
developments could delay or prevent the launch, commercialization,
manufacturing, distribution and availability of COMETRIQ; the degree of
market acceptance of COMETRIQ; the extent to which coverage and
reimbursement for COMETRIQ will be available from third-party payors;
risks and uncertainties related to Exelixis’ compliance with applicable
regulatory requirements, including healthcare fraud and abuse laws and
post-marketing requirements; the company's dependence on third-party
vendors; market competition; the uncertainty of the regulatory approval
process; 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 September
28, 2012, filed with the Securities and Exchange Commission (SEC) on
November 7, 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.
Charles Butler, 650-837-7277
Investor Relations and