– 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 –
– Exelixis Receives $50 Million Upfront Payment and is
Eligible for Future Regulatory and Commercial Milestones –
SOUTH SAN FRANCISCO, Calif. & CAMBRIDGE, Mass. & OSAKA, Japan--(BUSINESS WIRE)--Jan. 30, 2017--
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/
Source: Exelixis, Inc.
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