– EC approval triggers $40 million milestone
payment to Exelixis under Collaboration Agreement with Ipsen
–
– Exelixis’ supplemental New Drug
Application for CABOMETYX for previously treated advanced HCC
currently in review with the U.S. Food and Drug Administration
–
Exelixis, Inc. (Nasdaq: EXEL) today announced that its partner
Ipsen received approval from the European Commission (EC) for
CABOMETYX® (cabozantinib) tablets as a monotherapy for
hepatocellular carcinoma (HCC) in adults who have previously been
treated with sorafenib. This approval allows for the marketing of
CABOMETYX in this indication in all 28 member states of the
European Union, Norway and Iceland.
“The approval of CABOMETYX in the Europe Union is a very
important milestone for our partner Ipsen and marks significant
progress for people living with liver cancer, which is the
second-leading cause of cancer death worldwide,” said Michael M.
Morrissey, Ph.D., President and Chief Executive Officer of
Exelixis. “This patient community is in dire need of new options to
treat this aggressive disease, and we are excited to work with
Ipsen to make this treatment available to patients in the European
Union and other countries worldwide.”
Under the terms of the Collaboration Agreement
with Ipsen, Exelixis will receive a milestone
payment of $40 million for the approval of the
second-line treatment of HCC. This milestone will be paid
by Ipsen within the next 70 days.
“Today’s European Commission approval of CABOMETYX provides a
much-needed new option for HCC patients. Until now, physicians in
Europe had only one approved therapy for the second-line treatment
of this aggressive and difficult-to-treat cancer. We are proud to
offer CABOMETYX as an innovative treatment that has been shown to
extend survival in previously treated patients with HCC,” said
Harout Semerjian, Chief Commercial Officer of Ipsen. “This new
indication reinforces Ipsen’s commitment to improving patients’
lives through the expansion of the clinical benefit of CABOMETYX in
the treatment of solid tumors.”
The EC approval is based on results from the CELESTIAL trial of
CABOMETYX in patients with advanced HCC who received prior
sorafenib. In this phase 3 pivotal trial, CABOMETYX demonstrated a
statistically significant and clinically meaningful improvement in
overall survival (OS) versus placebo. CABOMETYX is also approved in
the European Union for the treatment of advanced renal
cell carcinoma (RCC) in adults who have received prior
VEGF-targeted therapy and for previously untreated intermediate- or
poor-risk advanced RCC.
On May 29, 2018, Exelixis announced that
the U.S. Food and Drug Administration (FDA) accepted for
filing the supplemental New Drug Application (sNDA) for CABOMETYX
for previously treated advanced HCC and assigned a Prescription
Drug User Fee Act action date of January 14, 2019. An sNDA is
an application to the FDA that, if approved, will allow a drug
sponsor to make changes to a previously approved product label,
including modifications to the indication.
About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled
study of cabozantinib in patients with advanced HCC conducted at
more than 100 sites globally in 19 countries. The trial was
designed to enroll 760 patients with advanced HCC who received
prior sorafenib and may have received up to two prior systemic
cancer therapies for HCC and had adequate liver function.
Enrollment of the trial was completed in September 2017.
Patients were randomized 2:1 to receive 60 mg of cabozantinib once
daily or placebo and were stratified based on etiology of the
disease (hepatitis C, hepatitis B or other), geographic region
(Asia versus other regions) and presence of extrahepatic
spread and/or macrovascular invasion (yes or no). No cross-over was
allowed between the study arms during the blinded treatment phase
of the trial. The primary endpoint for the trial is OS, and
secondary endpoints include objective response rate and PFS.
Exploratory endpoints include patient-reported outcomes, biomarkers
and safety.
In October 2017, Exelixis announced that the
independent data monitoring committee for the CELESTIAL study
recommended that the trial be stopped for efficacy following review
at the second planned interim analysis, with cabozantinib providing
a statistically significant and clinically meaningful improvement
in OS compared with placebo in patients with previously treated
advanced HCC. The data, originally presented at the 2018 American
Society of Clinical Oncology’s Gastrointestinal Cancers Symposium
(ASCO-GI) in January 2018, were published in The New
England Journal of Medicine in July 2018.1
About HCC
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.2 In the U.S., the incidence of liver cancer has
more than tripled since 1980.3 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 2018.3 HCC is the fastest-rising
cause of cancer-related death in U.S.4 Without treatment, patients
with advanced HCC usually survive less than 6 months.5
About the Exelixis and Ipsen Collaboration
In 2016, Exelixis granted Ipsen exclusive
rights for the commercialization and further clinical development
of cabozantinib outside of the United
States and Japan. Under the terms of the Collaboration
Agreement with Ipsen, Exelixis is entitled to
receive a tiered royalty of 22 percent to 26 percent of annual net
sales.
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in the United States for the
treatment of patients with advanced RCC. 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. 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.
Please see Important Safety Information below and full U.S.
prescribing information at
https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
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 stomatitis.
- 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
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 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, 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 tablets as a monotherapy in the
European Union for HCC in adults who have previously been treated
with sorafenib; Exelixis’ timing for receipt of a $40
million milestone payment from Ipsen for the
approval of CABOMETYX as a monotherapy in the European Union for
HCC in adults who have previously been treated with sorafenib;
Ipsen’s efforts to bring CABOMETYX to the liver cancer community
and its commitment to expanding the potential of CABOMETYX across
different indications; 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 and the availability of sufficient coverage and adequate
reimbursement for this product; Exelixis’ dependence on its
relationships with Ipsen, including Ipsen’s investment in the
resources necessary to successfully commercialize CABOMETYX in the
territories where it is approved and to execute its commercial
strategy; Exelixis’ continuing compliance with applicable legal and
regulatory requirements; Exelixis’ ability to protect its
intellectual property rights; Exelixis’ dependence on third-party
vendors for the 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 the ability
of Exelixis and its partners to obtain regulatory
approval for cabozantinib in new indications 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.
Exelixis, the Exelixis logo, CABOMETYX,
COMETRIQ and COTELLIC are registered U.S. trademarks.
__________________________
1 Abou-Alfa, G, Meyer T, Cheng AL, et al. Cabozantinib in patients
with advanced and progressing hepatocellular carcinoma. N Engl J
Med. 2018. 379:54-63.
2 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 2018.
3 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.
4 Mittal S, El-Serag HB. Epidemiology of HCC: Consider the
Population. Journal of Clinical Gastroenterology. 2013. 47:S2-S6. 5
Weledji E, Orock G, Ngowe M, Nsagha D. How grim is hepatocellular
carcinoma? Annals of Medicine and Surgery. 2014. 3:71-76.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20181114005991/en/
Investors Contact:Susan HubbardEVP, Public Affairs
andInvestor RelationsExelixis, Inc.(650)
837-8194shubbard@exelixis.comorMedia Contact:Lindsay
TreadwaySenior Director, Public Affairs and Advocacy
RelationsExelixis, Inc.(650) 837-7522ltreadway@exelixis.com
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