– In the phase 3 pivotal CELESTIAL trial, CABOMETYX demonstrated a
statistically significant and clinically meaningful overall survival
ALAMEDA, Calif.--(BUSINESS WIRE)--Sep. 21, 2018--
Inc. (NASDAQ:EXEL) today announced that its partner Ipsen received a
positive opinion from the Committee for Medicinal Products for Human Use
(CHMP), the scientific committee of the European Medicines Agency (EMA),
for CABOMETYX® (cabozantinib) tablets as a monotherapy for
the treatment of hepatocellular carcinoma (HCC) in adults who have been
previously treated with sorafenib. The positive CHMP opinion will now be
reviewed by the European Commission, which has the authority to approve
medicines for the European Union.
“This positive CHMP opinion represents significant progress for patients
in Europe with this aggressive form of liver cancer who progress on
prior systemic therapy, a large underserved patient population that
currently only has one approved second-line treatment option,” said
Michael M. Morrissey, Ph.D., President and Chief Executive Officer of
Exelixis. “We are excited about the potential therapeutic benefits
CABOMETYX may offer the liver cancer community and look forward to the
European Commission’s decision.”
Under the terms of the Collaboration Agreement with Ipsen, Exelixis is
eligible to receive a milestone payment of $40 million for the approval
of the second-line treatment of HCC. This milestone would be paid by
Ipsen within 70 days of the approval decision by the European Commission.
CABOMETYX is currently 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. The CHMP recommendation to expand the indication
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.
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 (PDUFA) 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.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
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 2018.4 HCC is the fastest-rising cause of cancer-related
death in U.S.1 Without treatment, patients with advanced HCC
usually survive less than 6 months.4
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 and South Korea
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; and in Canada for adult
patients with advanced RCC who have received prior VEGF targeted
therapy. In March 2017, the FDA granted orphan drug designation to
cabozantinib for the treatment of advanced HCC. On March 28, 2018, Ipsen
announced that the European Medicines Agency validated its application
for a new indication for cabozantinib as a treatment for previously
treated advanced HCC in the European Union; on September 20, 2018 the
CHMP provided a positive opinion for CABOMETYX as a monotherapy for the
treatment of HCC in adults who have been previously 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.
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. In July 2018, Exelixis was added to
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,
on Twitter or like Exelixis,
Inc. on Facebook.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the regulatory review process
in the European Union; the therapeutic potential of CABOMETYX as a
treatment option for adult patients in the European Union with advanced
HCC who have been previously treated with sorafenib; Exelixis’
eligibility to receive a $40 million milestone payment from Ipsen for
the approval of CABOMETYX as a treatment for previously treated advanced
HCC in the European Union, and the timing for receipt of such payment;
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: risks and uncertainties related to regulatory review and
approval processes, including that the European Commission may not
approve cabozantinib as a treatment for previously treated advanced HCC;
unexpected concerns that may arise as a result of the occurrence of
adverse safety events or additional data analyses of clinical trials
evaluating cabozantinib; Exelixis’ dependence on its relationships with
its collaboration partners, including their pursuit of regulatory
approvals for cabozantinib in new indications and their adherence to
their obligations under relevant collaboration agreements; Exelixis’
ability to protect its intellectual property rights; market competition;
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 August 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.
2International 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 September 2018.
3American 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 September 2018.
4 Weledji E, Orock G, Ngowe M, NsaghaD. How grim is
hepatocellular carcinoma? Ann Med Surg. 2014. 3:71-76.
View source version on businesswire.com: https://www.businesswire.com/news/home/20180920006004/en/
Source: Exelixis, Inc.
EVP, Public Affairs and
Lindsay Treadway, 650-837-7522
Director, Public Affairs and