- Cabozantinib commercialized for medullary thyroid cancer (MTC)
and filed for advanced renal cell carcinoma (RCC) -
- $200 million upfront payment and subsequent regulatory and
commercial milestones -
SOUTH SAN FRANCISCO, Calif. & PARIS--(BUSINESS WIRE)--Feb. 29, 2016--
Exelixis, Inc. (NASDAQ:EXEL) and Ipsen (Euronext: IPN; ADR: IPSEY) today
jointly announced an exclusive licensing agreement for the
commercialization and further development of cabozantinib, Exelixis’
lead oncology drug. Under the agreement, Ipsen will have exclusive
commercialization rights for current and potential future cabozantinib
indications outside of the United States, Canada and Japan. This
agreement includes rights to COMETRIQ®, which is currently
approved in the European Union (EU) for the treatment of adult patients
with progressive, unresectable, locally advanced or metastatic medullary
thyroid cancer (MTC). The companies have agreed to collaborate on the
development of cabozantinib for current and potential future
indications. Exelixis will maintain exclusive commercial rights for
cabozantinib in the United States and Canada, and continue its
discussions to partner commercial rights in Japan.
Under the agreement, Exelixis will receive a $200 million upfront
payment. Exelixis is eligible to receive regulatory milestones,
including $60 million upon the approval of cabozantinib in Europe for
advanced renal cell carcinoma (RCC) and $50 million upon the filing and
approval of cabozantinib in Europe for advanced hepatocellular carcinoma
(HCC), as well as additional regulatory milestones for potential further
indications. The agreement also includes up to $545 million of potential
commercial milestones and provides for Exelixis to receive tiered
royalties up to 26% on Ipsen’s net sales of cabozantinib in its
territories.
Marc de Garidel, Chairman and Chief Executive Officer of Ipsen said:
“The robust results from the METEOR study in advanced renal cell
carcinoma demonstrate that cabozantinib has the potential to become a
key oncology product in Europe. This transaction will help Ipsen
accelerate the growth of the company and strengthen its oncology
footprint in Europe. We are excited to bring cabozantinib to patients
and clinicians around the world.”
Future commercial indications for cabozantinib could include advanced
HCC, the subject of CELESTIAL, an Exelixis-sponsored phase 3 pivotal
trial for which top-line results are anticipated in 2017. Additional
earlier-stage studies are under way through Exelixis’ collaboration with
the National Cancer Institute’s Cancer Therapy Evaluation Program
(NCI-CTEP), and its ongoing Investigator-Sponsored Trial (IST) program.
Through these two programs, there are more than 45 ongoing or planned
studies including trials in advanced RCC, bladder cancer, colorectal
cancer, non-small cell lung cancer, and endometrial cancer.
“In Ipsen, Exelixis has an ideal partner to maximize the potential for
cabozantinib to have a positive impact on the treatment of cancer on a
global basis,” said Michael M. Morrissey, Ph.D., President and Chief
Executive Officer of Exelixis. “Ipsen’s established international
oncology marketing presence, late-stage clinical development expertise
and shared vision with Exelixis for the franchise potential of
cabozantinib will accelerate cabozantinib’s commercialization in its
territories, while Exelixis remains focused on our launch in the United
States. While our immediate priority will be on advanced renal cell
carcinoma, Exelixis and Ipsen are committed to exploring and potentially
developing cabozantinib in a variety of cancer settings.”
Cabozantinib is a small molecule therapy that inhibits the activity of
tyrosine kinases including VEGF receptors, MET, AXL, and RET. Following
positive results from the METEOR global phase 3 pivotal trial, the
tablet form of cabozantinib is the subject of pending U.S. and EU
regulatory applications for use as a treatment for advanced RCC in
patients who have received one prior therapy. In the EU, the Marketing
Authorization Application (MAA) for cabozantinib in advanced RCC has
been accepted and granted accelerated assessment. With this designation,
the MAA is eligible for a 150-day review, versus the standard 210 days
(excluding clock stops when information is requested by the EMA).
Exelixis plans to transfer sponsorship of this MAA to Ipsen. Exelixis
also anticipates transitioning the commercialization rights to COMETRIQ®
outside the U.S. from Exelixis’ current international partner for
COMETRIQ®, Swedish Orphan Biovitrum AB (Sobi), to Ipsen, in
accordance with the terms of its agreement with Sobi. In March 2014, the
capsule form of cabozantinib was approved by the European Commission
under the trade name COMETRIQ for the treatment of patients with
progressive, unresectable, locally advanced or metastatic MTC.
About the METEOR Phase 3 Clinical Trial
METEOR is a global, randomized open-label trial that compares
cabozantinib to everolimus, a standard of care therapy, in 658 patients
with advanced RCC whose disease progressed following treatment with a
VEGF receptor (VEGFR) tyrosine kinase inhibitor (TKI). The trial’s
primary endpoint is progression-free survival (PFS), and secondary
endpoints include overall survival (OS) and objective response rate
(ORR). Patients were randomized 1:1 to receive 60 mg of cabozantinib or
10 mg of everolimus daily, and were stratified based on number of prior
VEGFR TKI therapies and on commonly applied RCC risk criteria. No
crossover was allowed.
As published in the New England Journal of Medicine, the trial
met its primary PFS and secondary ORR endpoints.1
Cabozantinib demonstrated a 42% reduction in the rate of disease
progression or death as compared with everolimus, with median PFS of 7.4
months versus 3.8 months for everolimus (Hazard Ratio [HR]=0.58, 95%
Confidence Interval [CI] 0.45-0.75, p<0.001).
Following a pre-planned interim analysis that showed a strong trend in
OS favoring cabozantinib (HR=0.67, 95% CI 0.51-0.89, p=0.005) but did
not reach statistical significance, Exelixis undertook a second interim
analysis after consulting with regulatory authorities. The results of
this second interim analysis demonstrated a highly statistically
significant and clinically meaningful increase in OS for cabozantinib.
Exelixis has shared these data with regulators and intends to present
them at a medical conference later this year.
Cabozantinib’s safety profile was similar to that of other VEGFR TKIs in
this patient population. The incidence of adverse events (any grade),
regardless of causality, was 100% with cabozantinib and more than 99%
with everolimus. Serious adverse events occurred in 40% of cabozantinib
patients and 43% of everolimus patients. The rate of treatment
discontinuation due to adverse events was low (~10%) in both treatment
arms.
About Advanced Renal Cell Carcinoma
The American Cancer Society’s 2015 statistics cite kidney cancer as
among the top ten most commonly diagnosed forms of cancer among both men
and women in the U.S.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; however, the five-year
survival rate for patients with advanced or late-stage metastatic RCC is
under 10 percent, with no identified cure for the disease.4
Until the introduction of targeted therapies into the RCC setting a
decade ago, treatments for metastatic RCC had historically been limited
to cytokine therapy (e.g., interleukin-2 and interferon). In the second-
and later-line settings, which encompass approximately 17,000
drug-eligible patients in the U.S. and 37,000 globally,5 two
small-molecule therapies and an immune checkpoint inhibitor have been
approved. The currently approved small-molecule agents have shown little
differentiation in terms of efficacy, demonstrating only modest PFS
benefit in patients refractory to sunitinib, a commonly-used first-line
therapy.
About Cabozantinib
Cabozantinib is currently marketed in capsule form under the brand name
COMETRIQ® in the United States for the treatment of
progressive, metastatic MTC, and in the European Union for the treatment
of adult patients with progressive, unresectable locally advanced or
metastatic MTC. COMETRIQ is not indicated for patients with RCC. In the
METEOR trial, and all other cancer trials currently underway, Exelixis
is investigating a tablet formulation of cabozantinib distinct from the
COMETRIQ capsule form. The tablet formulation of cabozantinib is the
subject of the NDA and MAA for advanced RCC.
Cabozantinib inhibits the activity of tyrosine kinases including VEGF
receptors, MET, AXL and RET. These receptor tyrosine kinases are
involved in both normal cellular function and in pathologic processes
such as oncogenesis, metastasis, tumor angiogenesis and maintenance of
the tumor microenvironment.
The European Commission granted COMETRIQ conditional approval for the
treatment of adult patients with progressive, unresectable locally
advanced or metastatic MTC. Similar to another drug approved in this
setting, the approved indication states that for patients in whom
Rearranged during Transfection (RET) mutation status is not known or is
negative, a possible lower benefit should be taken into account before
individual treatment decisions.
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
-
Serious and sometimes fatal gastrointestinal perforations and
fistulas occur in COMETRIQ-treated patients.
-
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated
patients.
-
COMETRIQ treatment results in an increase in thrombotic events, such
as heart attacks.
-
Wound complications have been reported with COMETRIQ.
-
COMETRIQ treatment results in an increase in hypertension.
-
Osteonecrosis of the jaw has been observed in COMETRIQ-treated
patients.
-
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients
treated with COMETRIQ.
-
The kidneys can be adversely affected by COMETRIQ. Proteinuria and
nephrotic syndrome have been reported in patients receiving COMETRIQ.
-
Reversible Posterior Leukoencephalopathy Syndrome has been observed
with COMETRIQ.
-
Avoid administration of COMETRIQ with agents that are strong CYP3A4
inducers or inhibitors.
-
COMETRIQ is not recommended for use in patients with moderate or
severe hepatic impairment.
-
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions
(≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia
syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue,
oral pain, hair color changes, dysgeusia, hypertension, abdominal pain,
and constipation. The most common laboratory abnormalities (≥25%) are
increased AST, increased ALT, lymphopenia, increased alkaline
phosphatase, hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Please see full U.S. prescribing information, including Boxed WARNINGS,
at www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf
Please refer to the full European Summary of Product Characteristics for
full European Union prescribing information, including contraindication,
special warnings and precautions for use at www.sobi.com
once posted.
About Ipsen
Ipsen is a global specialty-driven biotechnological 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 expenditure totaled close to €193 million,
representing about 13% of Group sales. The Group has more than 4,600
employees worldwide. Ipsen’s shares are traded on segment A of EuronextParis (stock code: IPN, ISIN code: FR0010259150) and 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 trade on the over-the-counter market in the
United States under the symbol IPSEY. For more information on Ipsen,
visit www.ipsen.com.
About Exelixis
Exelixis, Inc. is a biopharmaceutical company committed to developing
small molecule therapies for the treatment of cancer. Exelixis is
focusing its development and commercialization efforts primarily on
cabozantinib, an internally discovered inhibitor of multiple receptor
tyrosine kinases. Another Exelixis-discovered compound, COTELLIC™
(cobimetinib), a selective inhibitor of MEK, has been approved in
Switzerland, the United States, the European Union, and Canada, and is
being evaluated by Roche and Genentech (a member of the Roche Group) in
a broad global development program under a collaboration with Exelixis.
For more information, please visit the company’s website at www.exelixis.com.
Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the business and financial
terms of the collaboration agreement for cabozantinib with Ipsen,
including, the division of commercialization rights, development plans
and Exelixis’ eligibility to receive regulatory and commercial
milestones and royalties; Exelixis’ plan to continue its discussions to
partner commercial rights for cabozantinib in Japan; the potential for
cabozantinib to become a key oncology product in Europe and the impact
of the transaction on the growth of Ipsen; advanced HCC as a future
potential commercial indication for cabozantinib and the timing for
anticipated top-line results from CELESTIAL; the impact of the
collaboration with Ipsen on Exelixis’ plan to maximize the potential for
cabozantinib on a global basis; Exelixis’ plan to stay focused on the
potential launch of cabozantinib in advanced RCC in the United States;
advanced RCC as Exelixis’ immediate priority; Exelixis’ and Ipsen’s
commitment to exploring and potentially developing cabozantinib in a
variety of cancers; the eligibility for an expedited review of Exelixis’
MAA for cabozantinib in advanced RCC by the EMA and Exelixis’ plans to
transfer sponsorship of the MAA to Ipsen; Exelixis’ plans to transition
the commercialization rights to COMETRIQ outside of the U.S. from Sobi
to Ipsen; and Exelixis’ intent to present data from the second interim
analysis of OS for METEOR at a medical conference later this year. Words
such as “will,” “potential,” “future,” “continue,” “eligible,”
“priority,” “committed,” “plans,” “anticipates,” “intends,” 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: the clinical, therapeutic and commercial potential of
cabozantinib; 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; Exelixis’ ability to maintain its rights under the Ipsen
collaboration; risks and uncertainties related to regulatory review and
approval processes and Exelixis' compliance with applicable legal and
regulatory requirements; the ability to conduct clinical
trials of cabozantinib sufficient to achieve a positive completion;
Exelixis’ ability to judge the proper size and level of experience of
the commercialization teams required to support the launch of
cabozantinib for advanced RCC; unanticipated complications associated
with the transition of the COMETRIQ commercialization rights from Sobi
to Ipsen; the availability of data at the referenced times; 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’
quarterly report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on November 10, 2015, and in Exelixis’ future filings
with the SEC, including, without limitation, Exelixis’ annual report on
Form 10-K expected to be filed with the SEC on February 29, 2016. 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 Disclaimer
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
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements. Other risks and
uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and health care legislation; global
trends toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent in new
product development, including obtaining regulatory approval; the
Group's ability to accurately predict future market conditions;
manufacturing difficulties or delays; financial instability of
international economies and sovereign risk; dependence on the
effectiveness of the Group’s patents and other protections for
innovative products; and the exposure to litigation, including patent
litigation, and/or regulatory actions. The Group also depends on third
parties to develop and market some of its products which could
potentially generate substantial royalties; these partners could behave
in such ways which could cause damage to the Group’s activities and
financial results. The Group cannot be certain that its partners will
fulfill their obligations. It might be unable to obtain any benefit from
those agreements. A default by any of the Group’s partners could
generate lower revenues than expected. Such situations could have a
negative impact on the Group’s business, financial position or
performance. The Group expressly disclaims any obligation or undertaking
to update or revise any forward looking statements, targets or estimates
contained in this press release to reflect any change in events,
conditions, assumptions or circumstances on which any such statements
are based, unless so required by applicable law. The Group’s business is
subject to the risk factors outlined in its registration documents filed
with the French Autorité des Marchés Financiers.
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
trademarks, and COTELLIC is a U.S. trademark.
1Choueiri T.K. et al. N Engl J Med
2015;373:1814-23.
2Cancer Facts & Figures 2015. American Cancer Society.
Available at http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf
3Jonasch et al., BMJ (2014) vol. 349, g4797.
4http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-survival-rates
5ACS Cancer Facts and Figures 2015; Heng et al., Ann
Oncol (2012) vol. 23 no. 6; internal data on file; Motzer et al., N Engl
J Med (2007) vol. 356 no. 2; NCIN (UK) report, April 2014, Available at http://www.ncin.org.uk/view?rid=2676.
View source version on businesswire.com: http://www.businesswire.com/news/home/20160229006848/en/
Source: Exelixis, Inc.
Exelixis Contacts
Financial Community:
Susan
Hubbard, 650-837-8194
Investor Relations and Corporate
Communications
shubbard@exelixis.com
or
Media:
For
Exelixis, Inc.
Hal Mackins, 415-994-0040
hal@torchcomllc.com
or
Ipsen
Contacts
Media:
Didier Véron,
Tel.: +33 (0)1 58 33 51 16
Fax: +33 (0)1 58 33 50 58
Senior
Vice-Président, Public Affairs and Communication
didier.veron@ipsen.com
or
Financial
Community:
Stéphane Durant des Aulnois, Tel.: +33
(0)1 58 33 60 09
Fax: +33 (0)1 58 33 50 63
Vice
President, Investor Relations
stephane.durant.des.aulnois@ipsen.com
