PARIS -- (Business Wire)
Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the European
Commission (EC) has approved Cabometyx® (cabozantinib) 20,
40, 60 mg for the first-line treatment of adults with intermediate- or
poor-risk advanced renal cell carcinoma (aRCC). This approval allows for
the marketing of Cabometyx® (cabozantinib) in this indication
in all 28 member states of the European Union, Norway and Iceland.
“Today’s EC approval is a step forward for advanced kidney cancer
patients in Europe who will be able to access a new oral first-line
treatment option that offers significant improvement over the standard
of care,” saidHarout Semerjian, Executive Vice President,
Chief Commercial Officer, Ipsen.“Ipsen remains committed to
improving patients’ lives by continuing to develop new therapies and
expanding the potential of Cabometyx® across
Giuseppe Procopio, M.D., Head of the Genitourinary Unit at Fondazione
Istituto Nazionale Tumori Milan, stated: “The value of treatment
with Cabometyx® has been corroborated by the
data generated in clinical trials, and since 2016 physicians have also
witnessed the potential of it when treating patients following
VEGF-targeted therapy. For both of these reasons, physicians will be
pleased to soon have access to this new first-line treatment option for
intermediate- or poor-risk advanced RCC patients.”
Today’s decision is based on the CABOSUN trial, which demonstrated that
cabozantinib significantly prolongs progression-free survival (PFS)
compared to sunitinib in treatment-naive aRCC patients with
intermediate- or poor-risk. Cabozantinib is the first and only
monotherapy to demonstrate superior clinical efficacy over sunitinib in
treatment-naïve aRCC patients with intermediate- or poor-risk.
The detailed recommendations for the use of this product are described
in the Summary of Product Characteristics (SmPC), available here (https://cabometyx.eu/).
About the CABOSUN study
On May 23, 2016, Exelixis announced that CABOSUN met its primary
endpoint, demonstrating a statistically significant and clinically
meaningful improvement in PFS compared with sunitinib in patients with
intermediate- or poor-risk aRCC per IMDC (International Metastatic RCC
Carcinoma Database Consortium) criteria as determined by investigator
assessment. CABOSUN was conducted by The Alliance for Clinical Trials in
Oncology as part of Exelixis’ collaboration with the NCI-CTEP. These
results were first presented by Dr. Toni Choueiri at the meeting of the
European Society for Medical Oncology (ESMO) 2016, and published in the
Journal of Clinical Oncology (Choueiri, JCO, 2018).1
On June 19 2017 Exelixis announced that the analysis of the review by a
blinded independent radiology review committee (IRC) has confirmed the
primary efficacy endpoint results of investigator-assessed
progression-free survival (PFS) from the CABOSUN randomized phase 2
trial of cabozantinib as compared with sunitinib in patients with
previously untreated advanced renal cell carcinoma (RCC) with
intermediate- or poor-risk disease per the International Metastatic
Renal Cell Carcinoma Database Consortium (IMDC) criteria. Per the IRC
analysis, cabozantinib demonstrated a clinically meaningful and
statistically significant reduction in the rate of disease progression
or death as measured by PFS. The incidence of adverse events (any grade)
and the incidence of grade 3 or 4 adverse events between cabozantinib
and sunitinib were comparable.
CABOSUN is a randomized, open-label, active-controlled phase II trial
that enrolled 157 patients with aRCC determined to be intermediate- or
poor-risk per IMDC criteria. Patients were randomized 1:1 to receive
cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, four
weeks on followed by two weeks off). The primary endpoint was PFS.
Secondary endpoints included overall survival and objective response
rate. 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 IMDC criteria (Heng, JCO, 2009).2
Prior systemic treatment for RCC was not permitted.
About advanced Renal Cell Carcinoma
With the incidence predicted to rise 22% by 2020, renal cell carcinoma
(RCC) threatens to become one of the fastest growing cancers in the
world.3 Targeted therapies including tyrosine kinase
inhibitors (TKIs) of the VEGF receptor (VEGFR) introduced a decade ago,
significantly transformed the treatment landscape of aRCC.4
The American Cancer Society’s 2017 statistics cite kidney cancer as one
of the top ten most commonly diagnosed forms of cancer among both men
and women in the U.S.5 Clear cell RCC is the most common type
of kidney cancer in adults.6 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% with no identified cure for the disease.7
Approximately 30,000 patients in the U.S. and 68,000 globally require
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.9-10 These proteins promote tumor
angiogenesis (blood vessel growth), growth, invasiveness, and metastasis.11,12,13, 14 MET and AXL may provide escape pathways
that drive resistance to VEGFR inhibitors. 12 - 14
About CABOMETYX® (cabozantinib)
Cabometyx® is an oral small molecule inhibitor of receptors,
including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib
has been shown to inhibit the activity of these receptors, which are
involved in normal cellular function and pathologic processes such as
tumor angiogenesis, invasiveness, metastasis and drug resistance.
In February of 2016, Exelixis and Ipsen jointly announced an exclusive
licensing agreement for the commercialization and further development of
cabozantinib indications outside of the United States, Canada and Japan.
This agreement was amended in December of 2016 to include
commercialization rights for Ipsen in Canada. On April 25, 2016, the FDA
approved Cabometyx® tablets for the treatment of patients
with advanced RCC who have received prior anti-angiogenic therapy and on
September 9, 2016, the European Commission approved Cabometyx®
tablets for the treatment of advanced RCC in adults who have received
prior vascular endothelial growth factor (VEGF)-targeted therapy in the
European Union, Norway and Iceland. Cabometyx® is available
in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally,
On December 19, 2017, Exelixis received approval from the FDA for
Cabometyx® for the expanded indication of treatment of
On May 17, 2018, Ipsen announced that the European Commission approved
Cabometyx® for the first-line treatment of adults with
intermediate- or poor-risk advanced renal cell carcinomain the European
Union, Norway and Iceland.
Ipsen is a global specialty-driven biopharmaceutical group focused on
innovation and specialty care. The group develops and commercializes
innovative medicines in three key therapeutic areas - Oncology,
Neuroscience and Rare Diseases. Its commitment to oncology is
exemplified through its growing portfolio of key therapies for prostate
cancer, neuroendocrine tumors, renal cell carcinoma and pancreatic
cancer. Ipsen also has a well-established Consumer Healthcare business.
With total sales over €1.9 billion in 2017, Ipsen sells more than 20
drugs in over 115 countries, with a direct commercial presence in more
than 30 countries. Ipsen's R&D is focused on its innovative and
differentiated technological platforms located in the heart of the
leading biotechnological and life sciences hubs (Paris-Saclay, France;
Oxford, UK; Cambridge, US). The Group has about 5,400 employees
worldwide. Ipsen is listed in Paris (Euronext: IPN) and in the United
States through a Sponsored Level I American Depositary Receipt program
(ADR: IPSEY). For more information on Ipsen, visit www.ipsen.com.
Ipsen Forward Looking Statement
The forward-looking statements, objectives and targets contained herein
are based on the Group’s management strategy, current views and
assumptions. Such statements involve known and unknown risks and
uncertainties that may cause actual results, performance or events to
differ materially from those anticipated herein. All of the above risks
could affect the Group’s future ability to achieve its financial
targets, which were set assuming reasonable macroeconomic conditions
based on the information available today. Use of the words "believes,"
"anticipates" and "expects" and similar expressions are intended to
identify forward-looking statements, including the Group’s expectations
regarding future events, including regulatory filings and
determinations. Moreover, the targets described in this document were
prepared without taking into account external growth assumptions and
potential future acquisitions, which may alter these parameters. These
objectives are based on data and assumptions regarded as reasonable by
the Group. These targets depend on conditions or facts likely to happen
in the future, and not exclusively on historical data. Actual results
may depart significantly from these targets given the occurrence of
certain risks and uncertainties, notably the fact that a promising
product in early development phase or clinical trial may end up never
being launched on the market or reaching its commercial targets, notably
for regulatory or competition reasons. The Group must face or might face
competition from generic products that might translate into a loss of
market share. Furthermore, the Research and Development process involves
several stages each of which involves the substantial risk that the
Group may fail to achieve its objectives and be forced to abandon its
efforts with regards to a product in which it has invested significant
sums. Therefore, the Group cannot be certain that favorable results
obtained during pre-clinical trials will be confirmed subsequently
during clinical trials, or that the results of clinical trials will be
sufficient to demonstrate the safe and effective nature of the product
concerned. There can be no guarantees a product will receive the
necessary regulatory approvals or that the product will prove to be
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1 “Choueiri TK, Hessel C, Halabi S, et al. Cabozantinib
versus sunitinib as initial therapy for metastatic renal cell carcinoma
of intermediate or poor risk (Alliance A031203 CABOSUN randomised
trial): Progression-free survival by independent review and overall
survival update. Eur J Cancer. 2018;94:115-25.
2 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. Journal of Clinical Oncology. 2009;
3 Ferlay J, Soerjomataram I, Dikshit R, et al: Cancer
incidence and mortality worldwide: sources, methods and major patterns
in GLOBOCAN 2012. Int J Cancer 136:E359-86, 2015
4 Jacobsen J, Grankvist K, Rasmuson T, et al. Expression of
vascular endothelial growth factor protein in human renal cell
carcinoma. BJU Int. 2004;93:297–302.
5 American Cancer Society. Cancer Facts & Figures 2017.
Atlanta: American Cancer Society; 2017.
6 Jonasch E., Gao J., Rathmell W.K., Renal cell carcinoma.
BMJ. 2014; 349:g4797.
7 Ko, J. J., Choueiri, T.K., et al. First-, second-
third-line therapy for mRCC: benchmarks for trial design from the IMDC.
British Journal of Cancer. 2014; 110: 1917-1922.
8 Decision Resources Report: Renal Cell Carcinoma. October
2014 (internal data on file).
9 Harshman, L.C. and Choueiri, T.K., Targeting the hepatocyte
growth factor/c-Met signaling pathway in renal cell carcinoma. Cancer J.
10 Rankin et al., Direct regulation of GAS6/AXL signaling by
HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci U
S A. 2014; 111(37):13373-8.
11 Zhou L, Liu X-D, Sun M, et al. Targeting MET and AXL
overcomes resistance to sunitinib therapy in renal cell carcinoma.
12 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.
13 Takahashi A, Sasaki H, Kim SJ, 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.
14 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.
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