– In the phase 2 CABOSUN trial, CABOMETYX demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival versus sunitinib in patients with previously
untreated renal cell carcinoma –
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Mar. 23, 2018--
Inc. (NASDAQ:EXEL) today announced that its partner Ipsen has
received a positive opinion from the Committee for Medicinal Products
for Human Use (CHMP), the scientific committee of the European Medicines
Agency (EMA), for CABOMETYX® (cabozantinib) 20 mg, 40 mg and 60 mg for
the first-line treatment of adults with intermediate- or poor-risk
advanced renal cell carcinoma (RCC). The positive CHMP opinion will now
be reviewed by the European Commission, which has the authority to
approve medicines for the European Union.
“This positive CHMP opinion represents a significant step forward in
helping to address an unmet need for patients in Europe with
intermediate- or poor-risk advanced RCC, who often fare poorly and are
in need of new therapies to better control their disease,” said Michael
M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis.
“This is an important milestone in our collaboration with Ipsen as we
work together to bring CABOMETYX to more patients with advanced kidney
cancer and as we continue to study its potential in additional types of
Under the terms of the Collaboration and License Agreement with Ipsen,
Exelixis is eligible to receive a milestone payment of $50 million for
the approval of the first-line treatment of advanced RCC, of which
approximately $46 million will be recognized as collaboration revenue in
the first quarter 2018. This milestone will be paid by Ipsen within 70
days after notification of the approval decision by the European
CABOMETYX was approved in the European Union in September 2016 for the
treatment of advanced RCC in adults following prior vascular endothelial
growth factor (VEGF)-targeted therapy. The CHMP recommendation to expand
the indication is based on results of the CABOSUN trial, which met its
primary endpoint of improving progression-free survival (PFS) compared
with sunitinib in patients with previously untreated advanced RCC
determined to be intermediate- or poor-risk by the International
Metastatic RCC Database Consortium (IMDC) criteria. In December 2017,
the U.S. Food and Drug Administration (FDA) approved CABOMETYX for the
expanded indication of patients with advanced RCC based on the results
from the CABOSUN trial.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About the CABOSUN Study
On May 23, 2016, Exelixis announced that the phase 2 CABOSUN study met
its primary endpoint, demonstrating a statistically significant and
clinically meaningful improvement in PFS compared with sunitinib in
patients with advanced intermediate- or poor-risk RCC as determined by
investigator assessment. The CABOSUN study was conducted by The Alliance
for Clinical Trials in Oncology and was sponsored by the National Cancer
Institute-Cancer Therapy Evaluation Program (NCI-CTEP) under the
Cooperative Research and Development Agreement with Exelixis for the
development of cabozantinib. These results were first presented by Dr.
Toni Choueiri at the European Society for Medical Oncology (ESMO) 2016
Congress, and published in the Journal of Clinical Oncology
(Choueiri, JCO, 2016).1 In June 2017, a blinded
independent radiology review committee (IRC) confirmed that cabozantinib
provided a clinically meaningful and statistically significant
improvement in the primary efficacy endpoint of investigator-assessed
PFS. Results from the IRC review were presented by Dr. Toni Choueiri at
the ESMO 2017 Congress.
CABOSUN was a randomized, open-label, active-controlled phase 2 trial
that enrolled 157 patients with advanced RCC determined to be
intermediate- or poor-risk by the IMDC criteria. Patients were
randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib
(50 mg once daily, 4 weeks on followed by 2 weeks off). The primary
endpoint was PFS. Secondary endpoints included overall survival,
objective response rate and safety. Eligible patients were required to
have locally advanced or metastatic clear-cell RCC, ECOG performance
status 0-2 and had to be intermediate- or poor-risk per the IMDC
criteria (Heng, JCO, 2009).2 Prior systemic treatment
for RCC was not permitted.
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.3 Clear cell RCC is the most common type
of kidney cancer in adults.4 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.3
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 kidney cancer.5
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.6,7 These proteins promote tumor angiogenesis
(blood vessel growth), growth, invasiveness and metastasis.8,9,10,11
MET and AXL may provide escape pathways that drive resistance to VEGF
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. 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.
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 regulatory review process
in the European Union; the therapeutic potential of CABOMETYX as a
treatment for patients in Europe with intermediate- or poor-risk
advanced RCC; Exelixis’ plan to work with Ipsen to bring CABOMETYX to
more patients with advance kidney cancer and study its potential in
additional types of cancer; Exelixis’ eligibility to receive a $50
million milestone payment from Ipsen for the approval of the first-line
treatment of RCC, and the related timing for receipt of such payment and
revenue recognition requirements; 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 “will,” “continue,” “eligible,” “commitment,” “potential,”
“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: risks and
uncertainties related to regulatory review and approval processes;
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; the level of
costs associated with Exelixis’ commercialization, research and
development, in-licensing or acquisition of product candidates, and
other activities; 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’ 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
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
Choueiri, T.K., et al. Cabozantinib versus Sunitinib as Initial
Targeted Therapy for Patients with Metastatic Renal Cell Carcinoma
of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. Am
J Clin Oncol. 2016; 35:591-597.
Heng D.Y., Xie W., Regan M.M., et al. Prognostic factors for overall
survival in patients with metastatic renal cell carcinoma treated
with vascular endothelial growth factor-targeted agents: Results
from a large, multicenter study. Am J Clin Oncol. 2009; 27:5794-5799.
American Cancer Society. Cancer Facts & Figures 2018. Atlanta:
American Cancer Society; 2018.
Jonasch, E., Gao, J., Rathmell, W. Renal cell carcinoma. BMJ. 2014;
Decision Resources Report: Renal Cell Carcinoma. October 2014
(internal data on file).
Harshman, L., and Choueiri, T. Targeting the hepatocyte growth
factor/c-Met signaling pathway in renal cell carcinoma. Cancer J.
Rankin, et al. Direct regulation of GAS6/AXL signaling by HIF
promotes renal metastasis through SRC and MET. Proc Natl Acad Sci
USA. 2014; 111:13373-13378.
Zhou, L., Liu, X-D., Sun, M., et al. Targeting MET and AXL overcomes
resistance to sunitinib therapy in renal cell carcinoma. Oncogene.
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.
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; 54:4233-4237.
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/20180322006323/en/
Source: Exelixis, Inc.
EVP, Public Affairs and
Lindsay Treadway, 650-837-7522
Director, Public Affairs and Advocacy Relations