— Approval based on results of two clinical
trials in patients with advanced hepatocellular carcinoma who had
received prior systemic therapy —
Exelixis, Inc. (NASDAQ: EXEL) today announced that Takeda
Pharmaceutical Company Limited (Takeda), its partner responsible
for the clinical development and commercialization of CABOMETYX®
(cabozantinib) in Japan, received approval from the Japanese
Ministry of Health, Labor and Welfare to manufacture and market
CABOMETYX as a treatment for patients with unresectable
hepatocellular carcinoma (HCC) that has progressed after prior
systemic therapy.
Takeda’s application is based on the results of two clinical
trials in patients with advanced HCC who had received prior
systemic therapy: CELESTIAL (XL184-309), a global, randomized,
placebo-controlled, double-blind phase 3 clinical trial, and
Cabozantinib-2003, a phase 2 clinical trial conducted in Japan. The
CELESTIAL trial was the basis for the CABOMETYX approvals in the
U.S. and the EU for the treatment of patients with HCC who have
been previously treated with sorafenib.
“Hepatocellular carcinoma causes approximately 30,000 deaths in
Japan each year and is a leading cause of cancer-related death
worldwide,” said Michael M. Morrissey, Ph.D., President and Chief
Executive Officer of Exelixis. “The approval of CABOMETYX in Japan
is an exciting next step toward bringing this treatment to liver
cancer patients who otherwise have limited treatment options
following prior systemic therapy. We’re proud to collaborate with
Takeda as we work to bring this treatment to patients in
Japan.”
Per the terms of Exelixis and Takeda’s collaboration and license
agreement, Exelixis is eligible to receive a $15 million milestone
payment from Takeda upon the first commercial sale of CABOMETYX for
unresectable HCC, which is expected to occur in the fourth quarter
of 2020. In January 2020, Takeda’s application for approval to
manufacture and sell CABOMETYX as a treatment for patients with
unresectable HCC that had progressed after prior systemic therapy
in Japan triggered a $10 million milestone payment. Exelixis
continues to be eligible to receive additional development,
regulatory and first-sale milestones for potential future
cabozantinib indications and is also eligible for sales revenue
milestones and royalties on net sales of cabozantinib in Japan.
Takeda fully funds cabozantinib development activities that are
exclusively for the benefit of Japan and has the opportunity to
share the costs associated with global cabozantinib clinical
trials, providing the company opts into those trials.
About HCC
Liver cancer is a 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 43,000 new cases in
the U.S. in 2020.2 HCC is the fastest-rising cause of
cancer-related death in the U.S.3 Without treatment, patients with
advanced HCC usually survive less than 6 months.4
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of
patients with advanced RCC and for the treatment of patients with
HCC who have been previously treated with sorafenib. CABOMETYX
tablets have also received regulatory approvals in the European
Union and additional countries and regions worldwide. In 2016,
Exelixis granted Ipsen exclusive rights for the commercialization
and further clinical development of cabozantinib outside of the
United States and Japan. In 2017, Exelixis granted exclusive rights
to Takeda Pharmaceutical Company Limited for the commercialization
and further clinical development of cabozantinib for all future
indications in Japan. Exelixis holds the exclusive rights to
develop and commercialize cabozantinib in the United States.
U.S. Important Safety Information
Warnings and Precautions
Hemorrhage: Severe and fatal hemorrhages occurred with
CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5%
in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX
for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to
patients who have a recent history of hemorrhage, including
hemoptysis, hematemesis, or melena.
Perforations and Fistulas: Gastrointestinal (GI)
perforations, including fatal cases, occurred in 1% of CABOMETYX
patients. Fistulas, including fatal cases, occurred in 1% of
CABOMETYX patients. Monitor patients for signs and symptoms of
perforations and fistulas, including abscess and sepsis.
Discontinue CABOMETYX in patients who experience a Grade 4 fistula
or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of
thrombotic events. Venous thromboembolism occurred in 7% (including
4% pulmonary embolism) and arterial thromboembolism in 2% of
CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX
patients. Discontinue CABOMETYX in patients who develop an acute
myocardial infarction or serious arterial or venous thromboembolic
event requiring medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause
hypertension, including hypertensive crisis. Hypertension occurred
in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do
not initiate CABOMETYX in patients with uncontrolled hypertension.
Monitor blood pressure regularly during CABOMETYX treatment.
Withhold CABOMETYX for hypertension that is not adequately
controlled with medical management; when controlled, resume at a
reduced dose. Discontinue CABOMETYX for severe hypertension that
cannot be controlled with anti-hypertensive therapy or for
hypertensive crisis.
Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients.
Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold
CABOMETYX until improvement to Grade 1 and resume at a reduced dose
for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be
managed with standard antidiarrheal treatments, or Grade 4
diarrhea.
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in
44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX
patients. Withhold CABOMETYX until improvement to Grade 1 and
resume at a reduced dose for intolerable Grade 2 PPE or Grade 3
PPE.
Proteinuria: Proteinuria occurred in 7% of CABOMETYX
patients. Monitor urine protein regularly during CABOMETYX
treatment. Discontinue CABOMETYX in patients who develop nephrotic
syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of
CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis,
osteitis, bone erosion, tooth or periodontal infection, toothache,
gingival ulceration or erosion, persistent jaw pain, or slow
healing of the mouth or jaw after dental surgery. Perform an oral
examination prior to CABOMETYX initiation and periodically during
treatment. Advise patients regarding good oral hygiene practices.
Withhold CABOMETYX for at least 3 weeks prior to scheduled dental
surgery or invasive dental procedures, if possible. Withhold
CABOMETYX for development of ONJ until complete resolution.
Impaired Wound Healing: Wound complications occurred with
CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to
elective surgery. Do not administer CABOMETYX for at least 2 weeks
after major surgery and until adequate wound healing is observed.
The safety of resumption of CABOMETYX after resolution of wound
healing complications has not been established.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
RPLS, a syndrome of subcortical vasogenic edema diagnosed by
characteristic findings on MRI, can occur with CABOMETYX. Evaluate
for RPLS in patients 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.
Advise pregnant women and females of reproductive potential of the
potential risk to a fetus. Verify the pregnancy status of females
of reproductive potential prior to initiating CABOMETYX and advise
them to use effective contraception during treatment and for 4
months after the last dose.
Adverse Reactions
The most commonly reported (≥25%) adverse reactions are:
diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension,
and vomiting.
Drug Interactions
Strong CYP3A4 Inhibitors: If coadministration with strong
CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong
CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Avoid St. John’s wort.
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed during
CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with 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
https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About Exelixis
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 system genetics, 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. Our discovery efforts have resulted in four commercially
available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO®
(esaxerenone), and we 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 the 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, follow @ExelixisInc on Twitter or like Exelixis,
Inc. on Facebook.
Forward-Looking Statements
This press release contains forward-looking statements,
including, without limitation, statements related to: the
therapeutic potential of CABOMETYX for patients with liver cancer
and Exelixis’ and Takeda’s collaboration to bring CABOMETYX to HCC
patients in Japan; Exelixis’ eligibility to receive a $15 million
milestone payment from Takeda upon Takeda’s first commercial sale
of CABOMETYX for unresectable HCC, which is expected to occur in
the fourth quarter of 2020; Exelixis’ eligibility for future
development, regulatory and first-sale milestones, plus sales
revenue milestones and royalties on net sales under its
collaboration with Takeda; 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: the degree of market acceptance of
CABOMETYX in Japan; Exelixis’ dependence on its relationship with
Takeda, including Takeda’s investment in the resources necessary to
successfully commercialize CABOMETYX in Japan; Exelixis’ and
Takeda’s ability to maintain and scale adequate sales, marketing,
market access and product distribution capabilities for their
products or to enter into and maintain agreements with third
parties to do so; Exelixis’ and Takeda’s continuing compliance with
applicable legal and regulatory requirements; the continuing
COVID-19 pandemic and its impact on Exelixis’ and Takeda’s
commercial activities; Exelixis’ ability to protect its
intellectual property rights; Exelixis’ dependence on third-party
vendors for the development, manufacture and supply of
cabozantinib; market competition, including the potential for
competitors to obtain approval for generic versions of CABOMETYX;
changes in economic and business conditions; and other factors
affecting Exelixis and its commercial programs and partnerships
discussed under the caption “Risk Factors” in Exelixis’ Quarterly
Report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on November 5, 2020, 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, except as required by law.
Exelixis, the Exelixis logo, CABOMETYX,
COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a
Japanese trademark.
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 November 2020. 2 American Cancer Society: Cancer Facts
& Figures 2020. Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.
Accessed November 2020. 3 Siegel R, Miller K, Jemal A: Cancer
Statistics, 2020. CA: A Cancer Journal for Clinicians. Volume 70,
Issue 1: 7-30. Available at:
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21590.
Accessed November 2020. 4 Weledji E, Orock G, Ngowe M, NsaghaD. How
grim is hepatocellular carcinoma? Ann Med Surg. 2014. 3:71-76.
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version on businesswire.com: https://www.businesswire.com/news/home/20201127005138/en/
Investors Contact: Susan Hubbard EVP, Public Affairs and
Investor Relations Exelixis, Inc. (650) 837-8194
shubbard@exelixis.com
Media Contact: Lindsay Treadway Senior Director, Public
Affairs and Advocacy Relations Exelixis, Inc. (650) 837-7522
ltreadway@exelixis.com
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