–
Takeda’s Rights to Include all Potential Indications for Cabozantinib,
which is Marketed in the U.S. and European Union for Renal Cell
Carcinoma and Medullary Thyroid Carcinoma –
SOUTH SAN FRANCISCO, Calif. & CAMBRIDGE, Mass. & OSAKA, Japan -Tuesday, January 31st 2017 [ ME NewsWire ]
– Exelixis Receives $50 Million Upfront Payment and is Eligible for Future Regulatory and Commercial Milestones –
(BUSINESS
WIRE)-- Exelixis, Inc. (NASDAQ:EXEL) and Takeda Pharmaceutical Company
Limited (TSE:4502) today announced an exclusive licensing agreement for
the commercialization and further clinical development in Japan of
cabozantinib, Exelixis’ lead oncology medicine. With the signing of the
agreement, Takeda gains exclusive commercial rights for all potential
future cabozantinib indications in Japan, including advanced renal cell
carcinoma (RCC), for which cabozantinib is marketed in the United States
and European Union as CABOMETYX™ tablets. The two companies will
collaborate on the future clinical development of cabozantinib in Japan.
Under
the terms of the agreement, Exelixis will receive a $50 million upfront
payment. Exelixis is eligible to receive development, regulatory, and
first-sales milestones of $95 million for the first three planned
indications. In addition, Exelixis will be eligible to receive royalties
on sales by Takeda.
“As an organization with a strong focus on
oncology innovation, our agreement with Exelixis brings a promising and
well-studied solid-tumor therapy to our pipeline that may help patients
in Japan suffering from RCC and potentially other equally devastating
cancers,” said Tsudoi Miyoshi, Head of Japan Oncology Business Unit of
Takeda. “We intend to pursue regulatory approval for RCC indications as
soon as we’re able, and look forward to commencing the local clinical
trial program to further strengthen the clinical profile of
cabozantinib.”
Exelixis and Takeda will partner on cabozantinib’s
clinical development in Japan and on translating existing and
forthcoming clinical data for potential regulatory filings in the
country. In the METEOR pivotal trial, cabozantinib demonstrated
statistically significant improvements in overall survival,
progression-free survival and objective response rate, meaningfully
differentiating it from other therapies to treat advanced renal cell
carcinoma following prior therapy. In addition to advanced RCC, future
indications could include advanced hepatocellular cancer (HCC), the
subject of the CELESTIAL global pivotal trial for which 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, and its ongoing
Investigator-Sponsored Trial 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.
“Takeda is the ideal partner to advance
cabozantinib in Japan and deliver this important treatment option to
Japanese patients with cancer,” said Michael M. Morrissey, Ph.D.,
President and Chief Executive Officer of Exelixis. “Takeda is widely
respected for both its clinical development and commercial expertise. We
look forward to supporting our new partner as it pursues Japanese
regulatory approval for cabozantinib, while simultaneously working
together to plan the next steps for clinical development in the country.
This agreement further propels the global progress for cabozantinib
development and commercialization, which now includes the recent first
commercial sale of CABOMETYX in the United Kingdom, triggering a $10
million milestone payment from Ipsen to Exelixis.”
Cabozantinib
is not approved for use in Japan. Previously, Exelixis and its
collaborators conducted early-stage clinical trials in Japan, including a
phase 1 trial in advanced solid tumors. Data from this trial were
presented at the European Society for Medical Oncology 2012 Congress and
the 2015 AACR-NCI-EORTC International Conference on Molecular Targets
and Cancer Therapeutics.1,2
Exelixis maintains its exclusive
rights to develop and commercialize cabozantinib in the United States,
and its partner Ipsen maintains its exclusive commercialization rights
for current and potential future cabozantinib indications outside of the
United States and Japan.
About CABOMETYX™ (cabozantinib) Tablets
CABOMETYX
is the tablet formulation of cabozantinib. Its 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.
CABOMETYX is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.
On
April 25, 2016, the FDA approved CABOMETYX tablets for the treatment of
patients with advanced renal cell carcinoma who have received prior
anti-angiogenic therapy. On September 9, 2016, the European Commission
approved CABOMETYX tablets for the treatment of advanced renal cell
carcinoma in adults who have received prior vascular endothelial growth
factor (VEGF)-targeted therapy in the European Union, Norway and
Iceland. 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, Exelixis and Ipsen jointly
announced an amendment to their exclusive licensing agreement for the
commercialization and development of cabozantinib to include Canada.
U.S. Important Safety Information
Hemorrhage:
Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3
hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in
everolimus-treated patients. Fatal hemorrhages also occurred in the
cabozantinib clinical program. Do not administer CABOMETYX to patients
that have or are at risk for severe hemorrhage.
Gastrointestinal
(GI) Perforations and Fistulas: Fistulas were reported in 1.2%
(including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of
everolimus-treated patients. GI perforations were reported in 0.9% of
CABOMETYX-treated patients and 0.6% of everolimus-treated patients.
Fatal perforations occurred in the cabozantinib clinical program.
Monitor patients for symptoms of fistulas and perforations. Discontinue
CABOMETYX in patients who experience a fistula that cannot be
appropriately managed or a GI perforation.
Thrombotic Events:
CABOMETYX treatment results in an increased incidence of thrombotic
events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated
patients and 2.5% of everolimus-treated patients. Pulmonary embolism
occurred in 3.9% of CABOMETYX-treated patients and 0.3% of
everolimus-treated patients. Events of arterial thromboembolism were
reported in 0.9% of CABOMETYX-treated patients and 0.3% of
everolimus-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. Hypertension was reported in 37% (15%
Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of
everolimus-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: Diarrhea occurred in 74% of patients
treated with CABOMETYX and in 28% of patients treated with everolimus.
Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2%
of everolimus-treated patients. 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. Dose modification due to
diarrhea occurred in 26% of patients.
Palmar-Plantar
Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia
syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and
in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2%
of CABOMETYX-treated patients and in <1% of everolimus-treated
patients. Withhold CABOMETYX in patients who develop intolerable Grade 2
PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a
reduced dose. Dose modification due to PPES occurred in 16% of
patients.
Reversible Posterior Leukoencephalopathy Syndrome
(RPLS): 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: CABOMETYX can cause fetal harm when administered to a
pregnant woman. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception
during treatment with CABOMETYX and for 4 months after the last dose.
Adverse
Reactions: The most commonly reported (≥25%) adverse reactions are:
diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension,
vomiting, weight decreased, and constipation.
Drug Interactions:
Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if
concomitant use with strong CYP3A4 inhibitors cannot be avoided.
Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4
inducers cannot be avoided.
Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.
Reproductive
Potential: Contraception―Advise females of reproductive potential to
use effective contraception during treatment with CABOMETYX and for 4
months after the final dose. Infertility ―CABOMETYX may impair fertility
in females and males of reproductive potential.
Hepatic
Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh
score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not
recommended for use in patients with severe hepatic impairment.
Please see full Prescribing Information at https://cabometyx.com/downloads/cabometyxuspi.pdf.
About Takeda Pharmaceutical Company
Takeda
Pharmaceutical Company Limited is a global, research and
development-driven pharmaceutical company committed to bringing better
health and a brighter future to patients by translating science into
life-changing medicines. Takeda focuses its R&D efforts on oncology,
gastroenterology and central nervous system therapeutic areas plus
vaccines. Takeda conducts R&D both internally and with partners to
stay at the leading edge of innovation. New innovative products,
especially in oncology and gastroenterology, as well as our presence in
Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda
employees are committed to improving quality of life for patients,
working with our partners in health care in more than 70 countries. For
more information, visit http://www.takeda.com/news.
Additional
information about Takeda is available through its corporate website,
www.takeda.com, and additional information about Takeda Oncology, the
brand for the global oncology business unit of Takeda Pharmaceutical
Company Limited, is available through its website,
www.takedaoncology.com.
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 EU) 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.
Exelixis Forward-Looking Statements
This
press release contains forward-looking statements, including, without
limitation, statements related to: the future clinical development of
cabozantinib by Exelixis and Takeda in Japan; Exelixis’ receipt of a $50
million upfront payment; Exelixis’ eligibility to receive development,
regulatory and first-sales milestones of $95 million for the first three
planned indications; Exelixis’ eligibility to receive royalties on
sales of cabozantinib by Takeda; the clinical and therapeutic potential
of cabozantinib for patients in Japan suffering from RCC and potentially
other cancers; Takeda’s intent to pursue regulatory approval for
cabozantinib in RCC indications and commence a local clinical trial
program; Exelixis’ and Takeda’s plan to translate existing and
forthcoming clinical data for potential regulatory filings in Japan;
advanced HCC as a potential future commercial indication; the timing of
anticipated results from CELESTIAL; the continued development of
cabozantinib through Exelixis’ collaboration with the National Cancer
Institute’s Cancer Therapy Evaluation Program, and its ongoing
Investigator-Sponsored Trial program; Exelixis’ intent to support Takeda
as it pursues Japanese regulatory approval for cabozantinib, while
simultaneously working together to plan the next steps for clinical
development in Japan; 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 “potential,” “further,” “will,” “eligible,” “planned,” “may,”
“intend,” “look forward,” “future,” “could,” “anticipated,” “next,”
“committed,” “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: the
complexities and challenges associated with regulatory review and
approval processes; Exelixis’ dependence on its relationship with
Takeda, including, the level of Takeda’s investment in the resources
necessary to successfully commercialize cabozantinib in Japan; the
degree of market acceptance of CABOMETYX and the availability of
coverage and reimbursement for CABOMETYX; 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 other collaborators,
including Ipsen with respect to cabozantinib in territories outside of
the United States and Japan and Genentech/Roche with respect to
cobimetinib; Exelixis’ dependence on third-party vendors; 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 3, 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.
Exelixis, the Exelixis logo, COMETRIQ and COTELLIC are registered U.S. trademarks,
and CABOMETYX is a U.S. trademark.
1
Nokihara et al., Molecular profile and anti-tumor activity in non-small
cell lung cancer (NSCLC) patients (pts) in a phase 1 study of
cabozantinib (XL184) in Japan. Ann Oncol. 2012; 23 (suppl 9):
ix152-ix174.
2 Nokihara et al., Final results of a phase 1 study
of cabozantinib (Cabo) in Japanese patients (pts) with expansion cohorts
in non-small cell lung cancer (NSCLC) with defined molecular
alterations. Mol Cancer Ther. December 1 2015 (14) (12 Supplement 2)
B179.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170130006192/en/
Contacts
Exelixis Contacts
Financial Community:
Susan Hubbard, 650-837-8194
EVP, Public Affairs and Investor Relations
shubbard@exelixis.com
or
Media:
For Exelixis, Inc.
Hal Mackins, 415-994-0040
hal@torchcomllc.com
or
Takeda Contacts
Japanese Media:
Tsuyoshi Tada, +81 (0) 3-3278-2417
tsuyoshi.tada@takeda.com
or
Media Outside Japan:
Amy Atwood, +1 617-444-2147
amy.atwood@takeda.com
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