– Approval based on statistically
significant and clinically meaningful overall survival benefit
demonstrated in the CELESTIAL phase 3 pivotal trial –
Exelixis, Inc. (NASDAQ:EXEL) today announced that its partner
Ipsen Biopharmaceuticals Canada Inc. received Health Canada
approval of CABOMETYX® (cabozantinib) tablets for the treatment of
patients with hepatocellular carcinoma (HCC) who have been
previously treated with sorafenib.
“Liver cancer is the fourth leading cause of cancer-related
death globally, and there is an urgent need for more treatment
options for patients living with this aggressive disease,” said
Michael M. Morrissey, Ph.D., President and Chief Executive Officer
of Exelixis. “The Health Canada approval of CABOMETYX brings a
much-needed new therapy to Canadian patients with liver cancer and
we look forward to our continued collaboration with Ipsen in our
efforts to make our medicines available to patients around the
world.”
The Health Canada approval was based on results from the
CELESTIAL phase 3 pivotal trial of CABOMETYX for patients with
advanced HCC who received prior treatment with sorafenib. CABOMETYX
demonstrated a statistically significant and clinically meaningful
improvement in overall survival (OS) versus placebo.
Under the terms of the Collaboration Agreement with Ipsen,
Exelixis will receive a milestone payment of $2 million for the
Health Canada approval.
CABOMETYX is also approved in Canada for the treatment of adult
patients with advanced renal cell carcinoma (RCC) who have received
prior vascular endothelial growth factor targeted therapy and for
the first-line treatment of adults with intermediate or poor risk
advanced RCC.
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 treatment with 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.
In October 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 analysis, with cabozantinib providing a
statistically significant and clinically meaningful improvement in
OS compared with placebo in patients with previously treated
advanced HCC. The data, originally presented at the 2018 American
Society of Clinical Oncology’s Gastrointestinal Cancers Symposium
(ASCO-GI) in January 2018, was published in The New England Journal
of Medicine in July 2018.1
About HCC
Liver cancer is a leading cause of cancer death worldwide,
accounting for more than 700,000 deaths and 800,000 new cases each
year.2 The Canadian Cancer Society estimates that 3,000 Canadians
will be diagnosed with liver cancer in 2019.3 In the U.S., the
incidence of liver cancer has more than tripled since 1980.4 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 2019.4 HCC
is the fastest-rising cause of cancer-related death in the U.S.5
Without treatment, patients with advanced HCC usually survive less
than 6 months.6
About the Exelixis and Ipsen Collaboration
In 2016, Exelixis granted Ipsen exclusive rights for the
commercialization and further clinical development of cabozantinib
outside of the United States and Japan. Under the terms of the
Collaboration Agreement with Ipsen, Exelixis is entitled to receive
a tiered royalty of 22 percent to 26 percent of annual net
sales.
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of
patients with advanced renal cell carcinoma and for the treatment
of patients with HCC who have been previously treated with
sorafenib. CABOMETYX tablets have also received regulatory
approvals in the European Union and additional countries and
regions worldwide. 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.
U.S. Important Safety Information
- Hemorrhage: Severe and fatal hemorrhages occurred with
CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5%
in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4
hemorrhage. Do not administer CABOMETYX to patients who have a
recent history of hemorrhage, including hemoptysis, hematemesis, or
melena.
- Perforations and Fistulas: GastrointestinaI (GI)
perforations, including fatal cases, occurred in 1% of CABOMETYX
patients. Fistulas, including fatal cases, occurred in 1% of
CABOMETYX patients. Monitor patients for signs and symptoms of
perforations and fistulas, including abscess and sepsis.
Discontinue CABOMETYX in patients who experience a fistula that
cannot be appropriately managed or a GI perforation.
- Thrombotic Events: CABOMETYX increased the risk of
thrombotic events. Venous thromboembolism occurred in 7% (including
4% pulmonary embolism) and arterial thromboembolism in 2% of
CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX
patients. Discontinue CABOMETYX in patients who develop an acute
myocardial infarction or serious arterial or venous thromboembolic
event requiring medical intervention.
- Hypertension and Hypertensive Crisis: CABOMETYX can
cause hypertension, including hypertensive crisis. Hypertension
occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX
patients. Do not initiate CABOMETYX in patients with uncontrolled
hypertension. Monitor blood pressure regularly during CABOMETYX
treatment. Withhold CABOMETYX for hypertension that is not
adequately controlled with medical management; when controlled,
resume at a reduced dose. Discontinue CABOMETYX for severe
hypertension that cannot be controlled with anti-hypertensive
therapy or for hypertensive crisis.
- Diarrhea: Diarrhea occurred in 63% of CABOMETYX
patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients.
Withhold CABOMETYX until improvement to Grade 1 and resume at a
reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea
that cannot be managed with standard antidiarrheal treatments, or
Grade 4 diarrhea.
- Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in
44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX
patients. Withhold CABOMETYX until improvement to Grade 1 and
resume at a reduced dose for intolerable Grade 2 PPE or Grade 3
PPE.
- Proteinuria: Proteinuria occurred in 7% of CABOMETYX
patients. Monitor urine protein regularly during CABOMETYX
treatment. Discontinue CABOMETYX in patients who develop nephrotic
syndrome.
- Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1%
of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis,
osteitis, bone erosion, tooth or periodontal infection, toothache,
gingival ulceration or erosion, persistent jaw pain, or slow
healing of the mouth or jaw after dental surgery. Perform an oral
examination prior to CABOMETYX initiation and periodically during
treatment. Advise patients regarding good oral hygiene practices.
Withhold CABOMETYX for at least 28 days prior to scheduled dental
surgery or invasive dental procedures. Withhold CABOMETYX for
development of ONJ until complete resolution.
- Wound Complications: Wound complications were reported
with CABOMETYX. Stop CABOMETYX at least 28 days prior to scheduled
surgery. Resume CABOMETYX after surgery based on clinical judgment
of adequate wound healing. Withhold CABOMETYX in patients with
dehiscence or wound healing complications requiring medical
intervention.
- Reversible Posterior Leukoencephalopathy Syndrome
(RPLS): RPLS, a syndrome of subcortical vasogenic edema
diagnosed by characteristic finding on MRI, can occur with
CABOMETYX. 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: CABOMETYX can cause fetal harm.
Advise pregnant women and females of reproductive potential of the
potential risk to a fetus. Verify the pregnancy status of females
of reproductive potential prior to initiating CABOMETYX and advise
them to use effective contraception during treatment and for 4
months after the last dose.
- Adverse Reactions: The most commonly reported (≥25%)
adverse reactions are: diarrhea, fatigue, decreased appetite, PPE,
nausea, hypertension, and vomiting.
- Strong CYP3A4 Inhibitors: If coadministration with
strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX
dosage. Avoid grapefruit or grapefruit juice.
- Strong CYP3A4 Inducers: If coadministration with strong
CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Avoid St. John’s wort.
- Lactation: Advise women not to breastfeed during
CABOMETYX treatment and for 4 months after the final dose.
- Hepatic Impairment: In patients with 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 system genetics, 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. Our discovery efforts have resulted in four commercially
available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO®
(esaxerenone), and we have entered into partnerships with leading
pharmaceutical companies to bring these important medicines to
patients worldwide. Supported by revenues from our marketed
products and collaborations, we are committed to prudently
reinvesting in our business to maximize the potential of our
pipeline. We are supplementing 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 is a member of Standard & Poor’s (S&P) MidCap 400
index, which measures the performance of profitable mid-sized
companies. For more information about Exelixis, please visit
www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis,
Inc. on Facebook.
Forward-Looking Statements
This press release contains forward-looking statements,
including, without limitation, statements related to: the potential
of CABOMETYX as a new therapy for Canadian patients with liver
cancer; Exelixis’ continued collaboration with Ipsen to make
Exelixis medicines available across different indications around
the world; the anticipated timing for receipt of a $2 million
milestone payment from Ipsen for the Health Canada approval; and
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. Any
statements that refer to expectations, projections or other
characterizations of future events or circumstances are
forward-looking statements and 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: the degree of market acceptance of CABOMETYX
and Ipsen’s ability to obtain or maintain coverage and
reimbursement for this product; Exelixis’ dependence on its
relationship with Ipsen, including Ipsen’s investment in the
resources necessary to successfully commercialize CABOMETYX in the
territories where it is approved; Exelixis’ and Ipsen’s continuing
compliance with applicable legal and regulatory requirements;
Exelixis’ ability to protect its intellectual property rights;
Exelixis’ dependence on third-party vendors for the manufacture and
supply of cabozantinib; market competition, including the potential
for competitors to obtain approval for generic versions of
CABOMETYX; changes in economic and business conditions; and other
factors affecting the ability of Exelixis and its commercial
programs and partnerships discussed under the caption “Risk
Factors” in Exelixis’ Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission (SEC) on October 30, 2019, and
in Exelixis’ future filings with the SEC. All forward-looking
statements in this press release are based on information available
to Exelixis as of the date of this press release, and Exelixis
undertakes no obligation to update or revise any forward-looking
statements contained herein.
Exelixis, the Exelixis logo, CABOMETYX,
COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a
Japanese trademark.
1 Abou-Alfa, G, Meyer T, Cheng AL, et al. Cabozantinib in
patients with advanced and progressing hepatocellular carcinoma. N
Engl J Med. 2018. 379:54-63. 2 International Agency for Research on
Cancer. GLOBOCAN 2018. Liver Fact Sheet. Available at:
http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed November 2019. 3 Canadian Cancer Society: Liver Cancer
Statistics. Available at:
https://www.cancer.ca/en/cancer-information/cancer-type/liver/statistics/?region=on.
Accessed November 2019. 4 American Cancer Society: Cancer Facts and
Figures 2019. Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf.
Accessed November 2019. 5 Mittal S, El-Serag HB. Epidemiology of
HCC: Consider the Population. J Clin Gastroenterol. 2013. 47:S2-S6.
6 Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular
carcinoma? Ann Med Surg. 2014. 3:71-76.
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version on businesswire.com: https://www.businesswire.com/news/home/20191112005303/en/
Investors: Susan Hubbard EVP, Public Affairs and Investor
Relations Exelixis, Inc. (650) 837-8194 shubbard@exelixis.com
Media: Lindsay Treadway Senior Director, Public Affairs
and Advocacy Relations Exelixis, Inc. (650) 837-7522
ltreadway@exelixis.com
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