– Approval based on the improvement in overall survival,
progression-free survival and objective response rate for CABOMETYX
versus everolimus in the phase 3 pivotal METEOR trial –
ALAMEDA, Calif.--(BUSINESS WIRE)--Sep. 19, 2018--
Inc. (NASDAQ:EXEL) today announced that its partner Ipsen
Biopharmaceuticals Canada Inc. received approval from Health Canada of
CABOMETYX® (cabozantinib) tablets for the treatment of adults
with advanced renal cell carcinoma (RCC) who have received prior
vascular endothelial growth factor (VEGF) targeted therapy. Health
Canada granted CABOMETYX priority review status, which provided an
accelerated review of Ipsen’s new drug submission.
“The approval of CABOMETYX in Canada helps address a significant unmet
need for patients with advanced kidney cancer whose disease has
progressed on first-line therapy and who have limited treatments
available,” said Michael M. Morrissey, Ph.D., President and Chief
Executive Officer of Exelixis. “We are glad to be partnering with Ipsen
to bring this much needed treatment option to these patients and look
forward to our continued collaboration.”
The Health Canada approval was based on results of the phase 3 pivotal
METEOR trial in which CABOMETYX provided a statistically significant and
clinically meaningful improvement in overall survival, progression-free
survival and objective response rate as compared with everolimus in
patients with advanced RCC who have received prior anti-angiogenic
Under the terms of the Collaboration Agreement with Ipsen, Exelixis will
receive a milestone payment of $5 million for the Health Canada
approval. The payment will be made by Ipsen within the next 70 days.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About Advanced Renal Cell Carcinoma
The American Cancer Society’s 2018 statistics cite kidney cancer as
among the top ten most commonly diagnosed forms of cancer among both men
and women in the U.S.1 The Canadian Cancer Society estimates
that kidney cancer is among the top ten most common forms of kidney
cancer in Canada, with approximately 6,600 new cases diagnosed in 2017.2
Clear cell RCC is the most common type of kidney cancer in adults.3 If
detected in its early stages, the five-year survival rate for RCC is
high; for patients with advanced or late-stage metastatic RCC, however,
the five-year survival rate is only 12 percent, with no identified cure
for the disease.4 Approximately 30,000 patients in the U.S.
and 68,000 globally require treatment, and an estimated 14,000 patients
in the U.S. each year are in need of a first-line treatment for advanced
The majority of clear cell RCC tumors have lower than normal levels of a
protein called von Hippel-Lindau, which leads to higher levels of MET,
AXL and VEGF.5,6 These proteins promote tumor angiogenesis
(blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET
and AXL may provide escape pathways that drive resistance to VEGF
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)
CABOMETYX tablets are approved in the United States for the treatment of
patients with advanced 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
VEGF-targeted therapy; in the European Union for previously untreated
intermediate- or poor-risk advanced RCC; and in Canada for adult
patients with advanced RCC who have received prior VEGF targeted
therapy. In March 2017, the FDA granted orphan drug designation to
cabozantinib for the treatment of advanced HCC. On March 28, 2018, Ipsen
announced that the European Medicines Agency validated its application
for a new indication for cabozantinib as a treatment for previously
treated advanced HCC in the European Union. 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 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 three
commercially available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib) and COTELLIC® (cobimetinib), and 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. In July 2018, Exelixis was added to
the 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.
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 option for patients in Canada with previously
treated advanced RCC who have received prior VEGF targeted therapy;
Exelixis’ plan to work with Ipsen to bring new treatment options to more
patients with difficult-to-treat cancers in Canada and around the world;
the timing for receipt of a $5 million milestone payment from Ipsen to
Exelixis for the approval of CABOMETYX in Canada; 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 the availability of sufficient
coverage and adequate reimbursement for this product; Exelixis’
dependence on its relationships with its collaboration partners,
including the level of their investment in the resources necessary to
successfully commercialize partnered compounds in the territories where
they are approved; Exelixis’ continuing compliance with applicable legal
and regulatory requirements; Exelixis’ dependence on third-party vendors
for the manufacture and supply of cabozantinib; Exelixis’ ability to
protect its 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 affecting 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 August 1, 2018, 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.
1 American Cancer Society: Cancer Facts and Figures 2018.
Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf.
Accessed September 2018.
2 Canadian Cancer Society:
Canadian Cancer Statistics – A 2018 Special Report on Cancer Incidence
by Stage. Available at: http://www.cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Canadian%20cancer%20statistics/Canadian-Cancer-Statistics-2018-EN.pdf?la=en.
Accessed September 2018.
3 Jonasch, E., Gao, J.,
Rathmell, W. Renal cell carcinoma. BMJ. 2014; 349:g4797.
Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal
data on file).
5 Harshman, L., and Choueiri, T.
Targeting the hepatocyte growth factor/c-Met signaling pathway in renal
cell carcinoma. Cancer J. 2013; 19:316-323.
Rankin, et al. Direct regulation of GAS6/AXL signaling by HIF promotes
renal metastasis through SRC and MET. Proc Natl Acad Sci USA.
7 Zhou, L., Liu, X-D., Sun, M.,
et al. Targeting MET and AXL overcomes resistance to sunitinib therapy
in renal cell carcinoma. Oncogene. 2016; 35:2687-2697.
Koochekpour, et al. The von Hippel-Lindau tumor suppressor gene inhibits
hepatocyte growth factor/scatter factor-induced invasion and branching
morphogenesis in renal carcinoma cells. Mol Cell Biol. 1999;
9 Takahashi, A., Sasaki, H., Kim, S., et
al. Markedly increased amounts of messenger RNAs for vascular
endothelial growth factor and placenta growth factor in renal cell
carcinoma associated with angiogenesis. Cancer Res. 1994;
10 Nakagawa, M., Emoto, A., Hanada, T.,
Nasu, N., Nomura, Y. Tubulogenesis by microvascular endothelial cells is
mediated by vascular endothelial growth factor (VEGF) in renal cell
carcinoma. Br J Urol. 1997; 79:681-687.
View source version on businesswire.com: https://www.businesswire.com/news/home/20180919005146/en/
Source: Exelixis, Inc.
EVP, Public Affairs and
Lindsay Treadway, 650-837-7522
Director, Public Affairs and Advocacy Relations