– In the pivotal phase 3 CELESTIAL trial, CABOMETYX provided a
statistically significant and clinically meaningful improvement versus
placebo in overall survival –
– Exelixis announced the completed submission of a supplemental
New Drug Application to the U.S. Food and Drug Administration for
CABOMETYX for previously treated patients with advanced hepatocellular
carcinoma on March 15 –
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Mar. 28, 2018--
Inc. (NASDAQ:EXEL) today announced that its partner Ipsen received
validation of the application for variation to the CABOMETYX®
(cabozantinib) marketing authorization from the European Medicines
Agency (EMA), the European regulatory authority, for the addition of a
new indication for patients with previously treated advanced
hepatocellular carcinoma (HCC). The filing is based on results of the
global pivotal phase 3 CELESTIAL trial, which met its primary endpoint
of overall survival (OS), with cabozantinib providing a statistically
significant and clinically meaningful improvement in OS compared with
placebo in patients with advanced HCC who had been previously treated
with sorafenib (pre-specified critical p-value ≤ 0.021).
“We are excited by the potential benefit CABOMETYX may offer patients in
the European Union diagnosed with previously treated advanced
hepatocellular carcinoma, a patient community that has very limited
treatment options,” said Michael M. Morrissey, Ph.D., President and
Chief Executive Officer of Exelixis. “This milestone represents
significant progress in our collaboration and development program with
Ipsen to expand the use of CABOMETYX to additional patient populations
outside of the currently approved indication.”
Under the terms of the Collaboration and License Agreement with Ipsen,
upon the acceptance of this filing, Exelixis earned a $10 million
milestone payment. Due to new revenue recognition standards the company
adopted in the first quarter of 2018, Exelixis will not record this
amount as revenue but expects the milestone to be paid by Ipsen in the
second quarter of this year.
On March 6, 2017, the U.S. Food and Drug Administration (FDA) granted
orphan drug designation to cabozantinib for the treatment of advanced
HCC. On October 16, 2017, Exelixis announced that the independent data
monitoring committee for the CELESTIAL study recommended that the trial
be stopped for efficacy following review at the second planned interim
On March 15, 2018, Exelixis announced the completed submission of a
supplemental New Drug Application (sNDA) to the FDA for CABOMETYX for
previously treated advanced HCC based on findings from CELESTIAL. An
sNDA is an application to the FDA that, if approved, will allow a drug
sponsor to make changes to a previously approved product label,
including modifications to the indication.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of
cabozantinib in patients with advanced HCC conducted at more than 100
sites globally in 19 countries. The trial was designed to enroll 760
patients with advanced HCC who received prior sorafenib and may have
received up to two prior systemic cancer therapies for HCC and had
adequate liver function. Enrollment of the trial was completed in
September 2017. Patients were randomized 2:1 to receive 60 mg of
cabozantinib once daily or placebo and were stratified based on etiology
of the disease (hepatitis C, hepatitis B or other), geographic region
(Asia versus other regions) and presence of extrahepatic spread and/or
macrovascular invasion (yes or no). No cross-over was allowed between
the study arms during the blinded treatment phase of the trial. The
primary endpoint for the trial is OS, and secondary endpoints include
objective response rate and progression-free survival. Exploratory
endpoints include patient-reported outcomes, biomarkers and safety.
Liver cancer is the second-leading cause of cancer death worldwide,
accounting for more than 700,000 deaths and nearly 800,000 new cases
each year.1 In the U.S., the incidence of liver cancer has
more than tripled since 1980.2 HCC is the most common form of
liver cancer, making up about three-fourths of the estimated nearly
42,000 new cases in the U.S. in 2018.2 HCC is the
fastest-rising cause of cancer-related death in U.S.3 Without
treatment, patients with advanced HCC usually survive less than 6 months.4
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in the United States for the treatment of
patients with advanced renal cell carcinoma (RCC). CABOMETYX tablets are
also approved in the European Union, Norway, Iceland, Australia,
Switzerland and South Korea for the treatment of advanced RCC in adults
who have received prior vascular endothelial growth factor
(VEGF)-targeted therapy. Ipsen also submitted to the EMA the regulatory
dossier for cabozantinib as a treatment for first-line advanced RCC in
the European Union on August 28, 2017; on March 23, 2018, the CHMP
provided a positive opinion for CABOMETYX for the first-line treatment
of intermediate- or poor-risk advanced RCC. In 2016, Exelixis granted
Ipsen exclusive rights for the commercialization and further clinical
development of cabozantinib outside of the United States and Japan. In
2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company
Limited for the commercialization and further clinical development of
cabozantinib for all future indications in Japan, including RCC.
CABOMETYX is not indicated for previously treated advanced HCC.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
U.S. Important Safety Information
Hemorrhage: Severe and fatal hemorrhages have occurred with
CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic
events was 3% in CABOMETYX-treated patients. Do not administer
CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC
studies, fistulas were reported in 1% of CABOMETYX-treated patients.
Fatal perforations occurred in patients treated with CABOMETYX. In RCC
studies, gastrointestinal (GI) perforations were reported in 1% of
CABOMETYX-treated patients. Monitor patients for symptoms of fistulas
and perforations, including abscess and sepsis. Discontinue CABOMETYX
in patients who experience a fistula which cannot be appropriately
managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased
incidence of thrombotic events. In RCC studies, venous thromboembolism
occurred in 9% (including 5% pulmonary embolism) and arterial
thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal
thrombotic events occurred in the cabozantinib clinical program.
Discontinue CABOMETYX in patients who develop an acute myocardial
infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment
results in an increased incidence of treatment-emergent hypertension,
including hypertensive crisis. In RCC studies, hypertension was
reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor
blood pressure prior to initiation and regularly during CABOMETYX
treatment. Withhold CABOMETYX for hypertension that is not adequately
controlled with medical management; when controlled, resume CABOMETYX
at a reduced dose. Discontinue CABOMETYX for severe hypertension that
cannot be controlled with anti-hypertensive therapy. Discontinue
CABOMETYX if there is evidence of hypertensive crisis or severe
hypertension despite optimal medical management.
Diarrhea: In RCC studies, diarrhea occurred in 74% of patients
treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients
treated with CABOMETYX. Withhold CABOMETYX in patients who develop
intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be
managed with standard antidiarrheal treatments until improvement to
Grade 1; resume CABOMETYX at a reduced dose.
Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies,
palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients
treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated
with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable
Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume
CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a
syndrome of subcortical vasogenic edema diagnosed by characteristic
finding on MRI, occurred in the cabozantinib clinical program. Perform
an evaluation for RPLS in any patient presenting with seizures,
headache, visual disturbances, confusion or altered mental function.
Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity may be associated with CABOMETYX. Advise
pregnant women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during CABOMETYX
treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse
reactions are: diarrhea, fatigue, nausea, decreased appetite,
hypertension, PPE, weight decreased, vomiting, dysgeusia, and
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4
inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4
inducers cannot be avoided, increase the CABOMETYX dosage.
Lactation: Advise women not to breastfeed while taking
CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic
impairment, reduce the CABOMETYX dosage. CABOMETYX is not
recommended for use in patients with severe hepatic impairment.
Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
Founded in 1994, Exelixis, Inc. (NASDAQ: EXEL) is a commercially
successful, oncology-focused biotechnology company that strives to
accelerate the discovery, development and commercialization of new
medicines for difficult-to-treat cancers. Following early work in model
genetic systems, we established a broad drug discovery and development
platform that has served as the foundation for our continued efforts to
bring new cancer therapies to patients in need. We discovered our lead
compounds, cabozantinib and cobimetinib, and advanced them into clinical
development before entering into partnerships with leading
biopharmaceutical companies in our efforts to bring these medicines to
patients globally. We are steadfast in our commitment to prudently
reinvest in our business to maximize the potential of our pipeline. We
intend to supplement our existing therapeutic assets with targeted
business development activities and internal drug discovery – all to
deliver the next generation of Exelixis medicines and help patients
recover stronger and live longer. Exelixis recently earned a spot on
Deloitte’s Technology Fast 500 list, a yearly award program honoring the
500 fastest-growing companies over the past four years. For more
information about Exelixis, please visit www.exelixis.com,
on Twitter or like Exelixis,
Inc. on Facebook.
Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the therapeutic potential of
CABOMETYX as a treatment for patients in the European Union diagnosed
with previously treated advanced HCC; Exelixis’ plan to work with Ipsen
to expand the use of CABOMETYX to additional patient populations outside
of the current approved indication; Exelixis’ expectations regarding the
timing of Ipsen’s $10 million milestone payment; Exelixis’ plans to
reinvest in its business to maximize the potential of the company’s
pipeline, including through targeted business development activities and
internal drug discovery; and Exelixis’ mission to deliver the next
generation of Exelixis medicines and help patients recover stronger and
live longer. Words such as “potential, “may,” “will,” “expects,”
“continue,” “commitment,” “intend,” 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. 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: Exelixis’ dependence on its relationships with Ipsen,
including, the level of Ipsen’s investment in the resources necessary to
successfully commercialize cabozantinib in the territories where it is
approved; market acceptance of CABOMETYX, COMETRIQ, and COTELLIC and the
availability of coverage and reimbursement for these products; the risk
that unanticipated developments could adversely affect the
commercialization of CABOMETYX, COMETRIQ, and COTELLIC; Exelixis’
dependence on third-party vendors for the development, manufacture and
supply of its products; the level of costs associated with Exelixis’
commercialization, research and development, in-licensing or acquisition
of product candidates, and other activities; competition in the area of
business development activities and the inherent uncertainty of the drug
discovery process; Exelixis’ ability to protect the company’s
intellectual property rights; market competition, including the
potential for competitors to obtain approval for generic versions of
Exelixis’ marketed products; changes in economic and business
conditions, and other factors discussed under the caption “Risk Factors”
in Exelixis’ annual report on Form 10-K filed with the Securities and
Exchange Commission (SEC) on February 26, 2018, and in Exelixis’ future
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, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
View source version on businesswire.com: https://www.businesswire.com/news/home/20180327006449/en/
Source: Exelixis, Inc.
Susan Hubbard, 650-837-8194
Public Affairs and Investor Relations
Senior Director, Public Affairs and