Ipsen and its Partner Exelixis Receive Positive CHMP Opinion for Cabometyx™ (Cabozantinib) for the Treatment of Advanced RCC in Adults Following Prior VEGF-Targeted Therapy

PARIS & SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Regulatory News:
Exelixis, Inc. (NASDAQ:EXEL) and Ipsen (Euronext: IPN; ADR: IPSEY) today
announced that the Committee for Medicinal Products for Human Use
(CHMP), the scientific committee of the European Medicines Agency (EMA)
provided a positive opinion for Cabometyx™ (cabozantinib) 20, 40, 60mg
for the treatment of advanced renal cell carcinoma (RCC) in adults
following prior vascular endothelial growth factor (VEGF)-targeted
therapy and recommended it for marketing authorization. The CHMP
positive opinion will now be reviewed by the European Commission (EC),
which has the authority to approve medicines for the European Union (EU).
David Meek, Chief Executive Officer of Ipsen, said: “We are
pleased that European patients with renal cell cancer may soon have
access to Cabometyx™. Ipsen is very proud to receive this
positive CHMP opinion for Cabometyx™, a new drug with unprecedented
clinical results in the treatment of advanced renal cell carcinoma.
Cabometyx™ has demonstrated robust and consistent benefits regardless of
prior treatment, location and extent of tumor metastases in previously
treated patients suffering from advanced renal cell carcinoma.”
“The positive CHMP opinion for Cabometyx™ is a significant milestone
for both Exelixis and Ipsen as we work together to bring this important
treatment option to patients with advanced renal cell carcinoma,” said
Michael M. Morrissey, Ph.D., President and Chief Executive Officer of
Exelixis. “With our shared mission of delivering innovative
therapies to improve the treatment of cancer, we have the opportunity to
change the way this patient population is treated. If approved by the
European Commission, Cabometyx™ will provide a new treatment option with
proven clinically significant benefit across all three efficacy
endpoints addressing a serious unmet medical need.”
The positive CHMP opinion was adopted following an accelerated review
procedure reserved for medicinal products expected to be of major public
health interest. The recommendation will now be reviewed by the European
Commission, which has the authority to approve medicines for use in the
28 countries of the European Union, Norway and Iceland, with a decision
expected two months post CHMP opinion.
The detailed recommendations for the use of this product will be
described in the Summary of Product Characteristics (SmPC), to be made
available if the medication receives marketing authorization from the
European Commission.
On January 28, 2016, the European Medicines Agency (EMA) validated
Exelixis’ Marketing Authorization Application (MAA) for Cabometyx™
(cabozantinib) as a treatment for patients with advanced renal cell
carcinoma who have received one prior therapy. The MAA has been granted
accelerated assessment, making it eligible for a 150-day review, versus
the standard 210 days. On February 29, 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.
On April 25, 2016 Cabometyx™ (cabozantinib) was approved by the U.S.
Food and Drug Administration (FDA) for the treatment of patients with
advanced RCC who have received prior anti-angiogenic therapy.
About the METEOR Phase 3 Pivotal Trial
METEOR was an
open-label, event-driven trial of 658 patients with advanced renal cell
carcinoma who had failed at least one prior VEGFR TKI therapy. The
primary endpoint was PFS in the first 375 patients treated. Secondary
endpoints included OS and objective response rate in all enrolled
patients. The trial was conducted at approximately 200 sites in 26
countries, and enrollment was weighted toward Western Europe, North
America, and Australia. Patients were randomized 1:1 to receive 60 mg of
Cabometyx™ (cabozantinib) daily or 10 mg of everolimus daily and were
stratified based on the number of prior VEGFR TKI therapies received and
on MSKCC risk criteria. No cross-over was allowed between the study arms.
METEOR met its primary endpoint of significantly improving PFS. Compared
with everolimus, Cabometyx™ (cabozantinib) was associated with a 42
percent reduction in the rate of disease progression or death. Median
PFS for Cabometyx™ (cabozantinib) was 7.4 months versus 3.8 months for
everolimus (HR=0.58, 95% CI 0.45-0.74, P<0.0001). Cabometyx™
(cabozantinib) also significantly improved the objective response rate
compared with everolimus (p<0.0001). These data were presented at the
European Cancer Congress in September 2015 and published in The
New England Journal of Medicine.¹
Cabometyx™ (cabozantinib) also demonstrated a statistically significant
and clinically meaningful increase in OS in the METEOR trial. Compared
with everolimus, Cabometyx™ (cabozantinib) was associated with a 34
percent reduction in the rate of death. Median OS was 21.4 months for
patients receiving Cabometyx™ (cabozantinib) versus 16.5 months for
those receiving everolimus (HR=0.66, 95% CI 0.53-0.83, P=0.0003).
Cabometyx™ (cabozantinib) benefit in OS was robust and consistent across
all pre-specified subgroups. In particular, benefit was observed
regardless of risk category, location and extent of tumor metastases,
and tumor MET expression level. These results were presented on June 5,
2016 at the ASCO Annual Meeting and concurrently published in The Lancet
Oncology.²
At the time of the analysis, the median duration of treatment in the
trial was 8.3 months with Cabometyx™ (cabozantinib) versus 4.4 months
with everolimus. The most frequent adverse events regardless of
causality were diarrhea, fatigue, decreased appetite and hypertension
for Cabometyx™ and fatigue, anemia, decreased appetite and cough for
everolimus. Dose reductions occurred for 62 percent and 25 percent of
patients, respectively. Discontinuation rate due to an adverse event not
related to disease progression was 12 percent with Cabometyx™
(cabozantinib) and 11 percent with everolimus.
About Advanced Renal Cell Carcinoma
Renal cell carcinoma
(RCC) represents 2-3% of all cancers³, with the highest
incidence occurring in Western countries. Generally, during the last two
decades until recently, there has been an annual increase of about 2% in
incidence both worldwide and in Europe, though in Denmark and Sweden a
continuing decrease has been observed⁴. In 2012, there were
approximately 84,400 new cases of RCC and 34,700 kidney cancer related
deaths within the European Union⁵. In Europe, overall
mortality rates for RCC have increased up until the early 1990s, with
rates generally stabilizing or declining thereafter⁶. There
has been a decrease in mortality since the 1980s in Scandinavian
countries and since the early 1990s in France, Germany, Austria, the
Netherlands, and Italy. However, in some European countries (Croatia,
Estonia, Greece, Ireland, Slovakia), mortality rates still show an
upward trend with increasing rates⁶.
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.^7,8 These proteins promote tumor angiogenesis
(blood vessel growth), growth, invasiveness and metastasis.^9-12
MET and AXL may provide escape pathways that drive resistance to VEGFR
inhibitors.^8,9
About CABOMETYX™ (cabozantinib)
Cabometyx™ (cabozantinib) targets
include MET, AXL and VEGFR-1, -2 and -3. 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.
About Exelixis
Exelixis, Inc. (NASDAQ: EXEL) is a
biopharmaceutical company committed to the discovery, development and
commercialization of new medicines with the potential to improve care
and outcomes for people with cancer. Since its founding in 1994, three
medicines discovered at Exelixis have progressed through clinical
development to receive regulatory approval. Currently, Exelixis is
focused on advancing cabozantinib, an inhibitor of multiple tyrosine
kinases including MET, AXL and VEGF receptors, which has shown clinical
anti-tumor activity in more than 20 forms of cancer and is the subject
of a broad clinical development program. Two separate formulations of
cabozantinib have received regulatory approval to treat certain forms of
kidney and thyroid cancer and are marketed for those purposes as
CABOMETYX™ tablets (U.S.) and COMETRIQ^® capsules (U.S. and
EU), respectively. Another Exelixis-discovered compound, COTELLIC™
(cobimetinib), a selective inhibitor of MEK, has been approved in major
territories including the United States and European Union, and is being
evaluated for further potential indications by Roche and Genentech (a
member of the Roche Group) under a collaboration with Exelixis. For more
information on Exelixis, please visit www.exelixis.com
or follow @ExelixisInc on Twitter.
About Ipsen
Ipsen is a global specialty-driven
pharmaceutical group with total sales exceeding €1.4 billion in 2015.
Ipsen sells more than 20 drugs in more than 115 countries, with a direct
commercial presence in more than 30 countries. Ipsen’s ambition is to
become a leader in specialty healthcare solutions for targeted
debilitating diseases. Its fields of expertise cover oncology,
neurosciences and endocrinology (adult & pediatric). Ipsen’s commitment
to oncology is exemplified through its growing portfolio of key
therapies improving the care of patients suffering from prostate cancer,
bladder cancer and neuro-endocrine tumors. Ipsen also has a significant
presence in primary care. Moreover, the Group has an active policy of
partnerships. Ipsen’s R&D is focused on its innovative and
differentiated technological platforms, peptides and toxins, located in
the heart of the leading biotechnological and life sciences hubs (Les
Ulis/Paris-Saclay, France; Slough/Oxford, UK; Cambridge, US). In 2015,
R&D expenditures neared €193 million. The Group has more than 4,600
employees worldwide. Ipsen’s shares are traded on segment A of Euronext
Paris (stock code: IPN, ISIN code: FR0010259150) and are eligible to the
“Service de Règlement Différé” (“SRD”). The Group is part of the SBF 120
index. Ipsen has implemented a Sponsored Level I American Depositary
Receipt (ADR) program, which trades on the over-the-counter market in
the United States under the symbol IPSEY. For more information on Ipsen,
visit www.ipsen.com.
Exelixis Forward-Looking Statement Disclaimer
This press
release contains forward-looking statements, including, without
limitation, statements related to: the review by the EC of the CHMP’s
positive opinion for Cabometyx^TM (cabozantinib) 20, 40, 60mg
for te treatment of advanced RCC in adults following prior VEGF-targeted
therapy; the potential for European patients with RCC to soon have
access to Cabometyx^TM; Exelixis’ shared mission with Ipsen to
deliver innovative therapies to improve the treatment of cancer; the
opportunity to change the way the RCC patient population is treated the
potential for Cabometyx™ to provide a new treatment option with proven
clinically significant benefit across all three efficacy endpoints
addressing a serious unmet medical need, if approved by the EC; the
expectation that the EC will issue a decision on the approval of
Cabometyx^TM in two months; Exelixis’ plan to work with
the European Commission to complete the review process for COMETRIQ’s
proposed indication as a treatment for progressive, unresectable locally
advanced or metastatic MTC; the potential approval by the European
Commission of the proposed indication of COMETRIQ for the treatment of
progressive, unresectable locally advanced or metastatic MTC;; Exelixis’
commitment to the discovery, development and commercialization of new
medicines with the potential to improve care and outcomes for people
with cancer; Exelixis’ focus on advancing cabozantinib; and the
continued development of cobimetinib. Words such as “will,” “may,”
“mission,” “opportunity,” “expected,” “committed,” “potential,”
“focused,” 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;
Exelixis’ dependence on its relationship with Ipsen, including, the
level of Ipsen’s investment in the resources necessary to successfully
commercialize cabozantinib in the territories where it is approved; the
risk that unanticipated developments could adversely affect the
commercialization of CABOMETYX; Exelixis’ ability to conduct clinical
trials of cabozantinib sufficient to achieve a positive completion;
risks related to the potential failure of cabozantinib to demonstrate
safety and efficacy in clinical testing; Exelixis’ dependence on its
relationship with Genentech/Roche with respect to cobimetinib and
Exelixis’ ability to maintain its rights under the collaboration;
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-Q filed with the Securities and Exchange
Commission (SEC) on May 4, 2016, 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.
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 favourable results obtained
during pre-clinical trials will be confirmed subsequently during
clinical trials, or that the results of clinical trials will be
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