– Accepted as a late-breaking oral
presentation at the 2018 American Society of Clinical Oncology’s
Gastrointestinal Cancers Symposium (ASCO-GI), January 18-20, 2018
–
– Exelixis to submit supplemental New Drug
Application to U.S. Food and Drug Administration (FDA) in the first
quarter of 2018 –
– Cabozantinib previously granted orphan
drug designation for the treatment of hepatocellular carcinoma
(HCC) by FDA –
Exelixis, Inc. (NASDAQ:EXEL) today announced that the phase 3
CELESTIAL trial results have been accepted as a late-breaking
presentation at the 2018 ASCO-GI Symposium, which is being held
January 18–20, 2018 in San Francisco. Detailed results from
CELESTIAL, the randomized, double-blind, placebo-controlled study
of cabozantinib versus placebo in patients with advanced HCC who
have received prior treatment with sorafenib, will be presented
during Oral Abstract Session B: Cancers of the Pancreas, Small
Bowel, and Hepatobiliary Tract, which begins at 2:15 p.m. PT on
Friday, January 19, 2018.
Oral Presentation
Abstract 207: Cabozantinib (C) versus placebo
(P) in patients (pts) with advanced hepatocellular carcinoma (HCC)
who have received prior sorafenib: results from the randomized
phase 3 CELESTIAL trial.
Ghassan K. Abou-Alfa, MD, Memorial
Sloan-Kettering Cancer Center, New York
On October 16, 2017, Exelixis announced that the CELESTIAL trial
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. The independent data monitoring committee for the
study recommended that the trial be stopped for efficacy following
review of the second planned interim analysis.
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.
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.
Based on available clinical trial data from various published
trials conducted in the second-line setting of advanced HCC, the
CELESTIAL trial statistics for the primary endpoint of OS assumed a
median OS of 8.2 months for the placebo arm. A total of 621 events
provide the study with 90 percent power to detect a 32 percent
increase in median OS (HR = 0.76) at the final analysis. Two
interim analyses were planned and conducted at 50 percent and 75
percent of the planned 621 events.
About HCC
Liver cancer is the third-leading cause of death worldwide, and
hepatocellular carcinoma (HCC) is the most common form, making up
about three-fourths of the nearly 41,000 cases that will be
diagnosed in 2017 in the U.S.1,2 Without treatment, patients with
advanced disease usually survive less than 6 months, and it is
estimated that 29,000 people will die due to liver cancer in the
U.S.3 Worldwide, nearly 800,000 new cases are diagnosed annually,
and the disease accounts for more than 700,000 deaths each
year.4
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in the United States for the
treatment of patients with advanced RCC who have received prior
anti-angiogenic therapy. CABOMETYX tablets are also approved in the
European Union, Norway and Iceland for the treatment of advanced
RCC in adults who have received prior vascular endothelial growth
factor (VEGF)-targeted therapy. 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 the treatment of 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
- Severe Hemorrhage occurred with
CABOMETYX. In two RCC studies, Grade ≥3 hemorrhagic events occurred
in 2.1% of CABOMETYX patients vs 1.6% with everolimus and in 5.1%
of CABOMETYX patients vs 1.4% with sunitinib. Fatal hemorrhages
also occurred in the cabozantinib clinical program. Do not
administer CABOMETYX to patients that have or are at risk for
severe hemorrhage.
- Gastrointestinal (GI) Perforations
and Fistulas were reported with CABOMETYX. In two RCC studies,
GI perforations occurred in 0.9% of CABOMETYX patients vs 0.6% with
everolimus and in 2.6% of CABOMETYX patients vs 0% with sunitinib.
Fatal perforations occurred in the cabozantinib clinical program.
Fistulas were reported in 1.2% (including 0.6% anal fistula) of
CABOMETYX patients vs 0% with everolimus. Monitor patients for
symptoms of perforations and fistulas. Discontinue CABOMETYX in
patients who experience a GI perforation or a fistula that cannot
be appropriately managed.
- Thrombotic Events increased with
CABOMETYX. In two RCC studies, arterial thromboembolism events were
reported in 0.9% of CABOMETYX patients vs 0.3% with everolimus and
1.3% of CABOMETYX patients vs 5.6% with sunitinib. Pulmonary
embolism events were reported in 3.9% of CABOMETYX patients vs 0.3%
with everolimus and 9% of CABOMETYX patients vs 0% with sunitinib.
Venous thromboembolism occurred in 7.3% of CABOMETYX patients vs
2.5% with everolimus. Fatal thrombotic events occurred in the
cabozantinib clinical program. Discontinue CABOMETYX in patients
who develop an acute myocardial infarction, cerebral infarction, or
other serious arterial thromboembolic complication.
- Hypertension and Hypertensive
Crisis occurred with CABOMETYX. In two RCC studies,
treatment-emergent hypertension increased with CABOMETYX.
Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX
patients vs 7.1% (3.1% Grade ≥3) with everolimus and in 67% (28%
Grade ≥3) of CABOMETYX patients vs 44% (21% Grade ≥3) with
sunitinib. 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 hypertensive crisis or severe hypertension that
cannot be controlled with antihypertensive therapy or medical
management.
- Diarrhea occurred with
CABOMETYX. In two RCC trials, diarrhea occurred in 74% (11% Grade
3) of CABOMETYX patients vs 28% (2% Grade 3) with everolimus and in
73% (10% Grade 3) of CABOMETYX patients vs 54% (11% Grade 3) with
sunitinib. 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
Syndrome (PPES) occurred with CABOMETYX. In two RCC trials,
PPES occurred in 42% (8.2% Grade 3) of CABOMETYX patients vs 6%
(<1% Grade 3) with everolimus and in 42% (7.7% Grade 3) of
CABOMETYX patients vs 33% (4.2% Grade 3) with sunitinib. Withhold
CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade
3 PPES 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. Evaluate for RPLS in
patients 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, PPES, weight decreased,
vomiting, dysgeusia, and stomatitis.
- Drug Interactions: Strong CYP3A4
inhibitors and inducers: Reduce the dosage of CABOMETYX if
concomitant use with strong CYP3A4 inhibitors cannot be avoided.
Increase the dosage of CABOMETYX if concomitant use with strong
CYP3A4 inducers cannot be avoided.
- 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.
About Exelixis
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 them 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 or follow
@ExelixisInc on Twitter.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements,
including, without limitation, statements related to: Exelixis’
plan to submit an supplemental New Drug Application to the FDA in
the first quarter of 2018 for cabozantinib as a treatment for
patients with advanced HCC; Exelixis’ plan to present the detailed
results from CELESTIAL at the 2018 ASCO-GI; Exelixis’ commitment to
reinvesting in its business to maximize the potential of its
pipeline, including supplementing its existing therapeutic assets
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 “to be,” “will,” “commitment,” “potential,”
“plan,” “mission,” 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: risks and
uncertainties related to regulatory review and approval processes
and Exelixis’ compliance with applicable legal and regulatory
requirements; the availability of data at the referenced time; the
level of costs associated with Exelixis’ commercialization,
research and development and other activities; competition in the
area of business development activities and the inherent
uncertainty of the drug discovery process; Exelixis’ ability and
the ability of its collaborators to conduct clinical trials of
cabozantinib and cobimetinib both alone and in combination with
other therapies sufficient to achieve a positive completion; risks
related to the potential failure of cabozantinib and cobimetinib
both alone and in combination with other therapies, to demonstrate
safety and efficacy in clinical testing; Exelixis’ dependence on
its relationships with its cabozantinib collaboration partners,
including, the level of their investment in the resources necessary
to successfully commercialize cabozantinib in the territories where
it is approved; Exelixis’ dependence on its relationship with
Genentech/Roche with respect to cobimetinib and Exelixis’
ability to maintain its rights under the collaboration; market
acceptance of CABOMETYX, COMETRIQ, and COTELLIC and the
availability of coverage and reimbursement for these products;
Exelixis’ dependence on third-party vendors for the development,
manufacture and supply of its products; Exelixis’ ability to
protect the company’s intellectual property rights; 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 1, 2017, 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.
References:
- Hepatocellular Carcinoma – United
States, 2001-2006. Morbidity and Mortality Weekly Report. Centers
for Disease Control and Prevention. Available at
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5917a3.htm. Accessed
November 2017.
- American Cancer Society: Cancer Facts
and Figures 2017. Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf.
Accessed November 2017.
- Weledji E, Orock G, Ngowe M, NsaghaD.
How grim is hepatocellular carcinoma? Annals of Medicine and
Surgery. 2014. (3):71-76.
- Estimated cancer incidence, mortality
and prevalence worldwide. International Agency for Research on
Cancer, GLOBOCAN 2012. Available at:
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed
November 2017.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20171121006072/en/
Investors:Exelixis, Inc.Susan Hubbard, 650-837-8194EVP,
Public Affairs and Investor
Relationsshubbard@exelixis.comorMedia:Exelixis, Inc.Claire
McConnaughey, 650-837-7052Senior Manager, Public
Affairscmcconn@exelixis.com
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