– 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 –
ALAMEDA, Calif.--(BUSINESS WIRE)--Nov. 15, 2018--
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
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
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
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.
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.
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.
View source version on businesswire.com: https://www.businesswire.com/news/home/20181114005991/en/
Source: Exelixis, Inc.
Public Affairs and Advocacy Relations