– Clinical trial will also explore single-agent activity of
cabozantinib in the first-line setting –
ALAMEDA, Calif. & PARIS--(BUSINESS WIRE)--Dec. 5, 2018--
Inc. (Nasdaq:EXEL) and Ipsen (Euronext:IPN; ADR:IPSEY) today
announced the initiation of COSMIC-312, a phase 3 pivotal trial of
cabozantinib (CABOMETYX®) in combination with atezolizumab
(TECENTRIQ®) versus sorafenib in previously untreated
advanced hepatocellular carcinoma (HCC). The co-primary endpoints of the
trial are progression-free survival and overall survival. An exploratory
arm will also evaluate cabozantinib monotherapy in this first-line
“Liver cancer is the fastest-rising cause of cancer-related death in the
U.S., underscoring the need for new treatment options for this patient
community,” said Gisela Schwab, M.D., President, Product Development and
Medical Affairs and Chief Medical Officer, Exelixis. “Based on past
evidence of potential synergistic effects with cabozantinib and immune
checkpoint inhibitors, the combination offers promise for patients with
advanced liver cancer who have not received prior treatment.”
COSMIC-312 is a multicenter, randomized, controlled phase 3 pivotal
trial that aims to enroll approximately 640 patients at up to 200 sites
globally. Patients will be randomized 6:3:1 to one of three arms:
cabozantinib (40 mg) and atezolizumab, sorafenib, or cabozantinib (60
Exelixis is sponsoring COSMIC-312, and Ipsen will co-fund the trial.
Ipsen will have access to the results to support potential future
regulatory submissions outside of the U.S. and Japan. Genentech, a
member of the Roche Group, is providing atezolizumab for use in this
“With more than 800,000 new diagnoses of liver cancer worldwide each
year and a poor prognosis for patients with advanced disease, there is
an urgent need to identify new treatment options,” said R. Kate Kelley,
M.D., Associate Professor of Clinical Medicine, Division of
Hematology/Oncology, University of California, San Francisco, and lead
investigator on COSMIC-312. “We look forward to learning whether the
combination of cabozantinib and atezolizumab may improve outcomes for
previously untreated patients.”
More information about this trial is available at ClinicalTrials.gov.
Liver cancer is the second-leading cause of cancer death worldwide,
accounting for more than 700,000 deaths and 800,000 new cases each year.1
In the U.S., the incidence of liver cancer has more than tripled since
1980.2 HCC is the most common form of liver cancer, making up
about three-fourths of the estimated nearly 42,000 new cases in the U.S.
in 2018.2 HCC is the fastest-rising cause of cancer-related
death in the U.S.3 According to the GLOBOCAN data, it is
estimated that across the European Union (EU-28) nearly 60,000 new
patients will be diagnosed with liver cancer in 2020.4
Without treatment, patients with advanced HCC usually survive less than
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in the United States for the treatment of
patients with renal cell carcinoma (RCC). On May 29, 2018, Exelixis
announced that the U.S. Food and Drug Administration (FDA) accepted for
filing the supplemental New Drug Application for CABOMETYX for
previously treated advanced HCC and assigned a Prescription Drug User
Fee Act action date of January 14, 2019. In March 2017, the FDA granted
orphan drug designation to cabozantinib for the treatment of advanced
CABOMETYX tablets are also approved in: the European Union, Norway,
Iceland, Australia, Switzerland, South Korea, Canada, Brazil and Taiwan
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; in Canada for adult patients
with advanced RCC who have received prior VEGF targeted therapy; and in
the European Union, Norway and Iceland for HCC in adults who have
previously been treated with sorafenib.
CABOMETYX is not indicated for previously untreated advanced HCC.
About Exelixis’ Collaboration with Ipsen
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 December 21, 2016, this agreement was amended to include
commercialization rights for Ipsen in Canada. Ipsen has opted to
participate in this phase 3 trial in first-line advanced HCC and will
have access to the results to support potential future regulatory
submissions. They may also participate in future studies at their
About Exelixis’ Collaboration with Takeda
On January 30, 2017, Exelixis and Takeda jointly announced an exclusive
licensing agreement for the commercialization and further development of
cabozantinib indications in Japan. Under the parties’ collaboration
agreement, if Takeda opts to participate in funding this phase 3 trial,
or future studies, Takeda will have access to the respective study
results to support potential future regulatory submissions in their
Exelixis holds the exclusive rights to develop and commercialize
cabozantinib in the United States.
Please see Important Safety Information below and full U.S. prescribing
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
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. Exelixis is a member of 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,
on Twitter or like Exelixis,
Inc. on Facebook.
Ipsen is a global 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.
Exelixis Forward-Looking Statements
This press release contains forward-looking statements, including,
without limitation, statements related to: the potential of the
combination of cabozantinib and atezolizumab, or of cabozantinib as a
monotherapy, as treatment options for patients with previously untreated
advanced HCC; 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: risks and uncertainties related to
regulatory review and approval processes and Exelixis’ compliance with
applicable legal and regulatory requirements; the potential failure of
the combination of cabozantinib and atezolizumab, or of cabozantinib as
a monotherapy, to demonstrate safety and/or efficacy in COSMIC-312;
uncertainties inherent in the product development process, including
evolving regulatory requirements, slower than anticipated patient
enrollment or inability to identify a sufficient number of clinical
trial sites; the costs of conducting clinical trials, including the
ability or willingness of Exelixis’ collaboration partners to invest in
the resources necessary to complete the trials; Exelixis’ dependence on
third-party vendors for the development, manufacture and supply of
cabozantinib; Exelixis’ ability to protect its intellectual property
rights; market competition; changes in economic and business conditions;
and other factors affecting Exelixis and its development programs
discussed under the caption “Risk Factors” in Exelixis’ Quarterly Report
on Form 10-Q filed with the Securities and Exchange Commission (SEC) on
November 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.
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
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
fulfil 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. The risks and
uncertainties set out are not exhaustive and the reader is advised to
refer to the Group’s 2017 Registration Document available on its website
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
TECENTRIQ® (atezolizumab) is a registered
trademark of Genentech, a member of the Roche Group.
The information stated above was prepared by Exelixis Inc. and Ipsen
and reflects solely the opinion of Exelixis and Ipsen. Nothing in this
statement shall be construed to imply any support or endorsement of
Exelixis or Ipsen, or any of its products, by the Regents of the
University of California, its officers, agents and employees.
1 International Agency for Research on Cancer. GLOBOCAN 2018.
Liver Fact Sheet. Available at: http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf. Accessed
2 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 November 2018.
3 Mittal S, El-Serag HB.
Epidemiology of HCC: Consider the Population. Journal of Clinical
Gastroenterology. 2013. 47:S2-S6.
International Agency for Research on Cancer (IARC). Cancer Tomorrow.
Accessed November 2018: http://globocan.iarc.fr/Pages/burden_sel.aspx
Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular
carcinoma? Annals of Medicine and Surgery. 2014. 3:71-76.
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Source: Exelixis, Inc.
EVP, Public Affairs
and Advocacy Relations
+44 (0) 1753 627721
Corporate External Communications