– Exelixis to submit a supplemental New Drug Application to the
U.S. Food and Drug Administration (FDA) in the first quarter of 2018;
cabozantinib previously granted orphan drug designation by FDA –
– Data to be submitted for presentation at an upcoming medical
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Oct. 16, 2017--
Inc. (NASDAQ:EXEL) today announced that its global phase 3 CELESTIAL
trial met its primary endpoint of overall survival (OS), with
cabozantinib providing a statistically significant and clinically
meaningful improvement in median OS compared to placebo in patients with
advanced hepatocellular carcinoma (HCC). The independent data monitoring
committee for the study recommended that the trial should be stopped for
efficacy following review of the second planned interim analysis.
CELESTIAL is a randomized, global phase 3 trial of cabozantinib versus
placebo in patients with advanced HCC who have been previously treated
with sorafenib. The safety data in the study were consistent with the
established profile of cabozantinib. Based on these results, Exelixis
plans to submit a supplemental New Drug Application (sNDA) to the U.S.
Food and Drug Administration (FDA) in the first quarter of 2018.
Detailed results from CELESTIAL will be submitted for presentation at a
future medical conference.
This press release features multimedia. View the full release here:
“We are excited that these positive results from the phase 3 CELESTIAL
trial bring us one step closer to the potential of offering previously
treated patients with this aggressive form of advanced liver cancer a
much-needed new treatment option,” said Gisela Schwab, M.D., President,
Product Development and Medical Affairs and Chief Medical Officer,
Exelixis. “This is an important milestone for the cabozantinib
development program; we are committed to studying cabozantinib in a
range of tumor types as part of our mission to deliver medicines that
improve treatment outcomes and give patients hope for the future.”
Exelixis will discuss the trial results with regulatory authorities and
determine next steps for the trial, including offering patients
currently receiving placebo the opportunity to cross over to
In March 2017, the FDA granted orphan drug designation to cabozantinib
for the treatment of advanced HCC. Orphan drug designation is granted to
treatments for diseases that affect fewer than 200,000 people in the
U.S. and provides certain incentives for medications intended for the
treatment, diagnosis or prevention of rare diseases. At present, these
incentives include seven years of marketing exclusivity for the orphan
indication, certain federal grants, tax credits, and waiver of certain
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.
The primary endpoint for the trial is OS, and secondary endpoints
include objective response rate and progression-free survival.
Exploratory endpoints include patient-reported outcomes, biomarkers and
Based on available clinical trial data from various published trials
conducted in the second-line setting of advanced HCC, the CELESTIAL
trial statistics for the primary endpoint of OS assumed a median OS of
8.2 months for the placebo arm. A total of 621 events provide the study
with 90 percent power to detect a 32 percent increase in median OS (HR =
0.76) at the final analysis. Two interim analyses were planned and
conducted at 50 percent and 75 percent of the planned 621 events.
Liver cancer is the third-leading cause of death
worldwide, and hepatocellular carcinoma (HCC) is the most common form,
making up about three-fourths of the nearly 41,000 cases that will be
diagnosed in 2017 in the U.S.1,2 Without treatment, patients
with advanced disease usually survive less than 6 months, and it is
estimated that 29,000 people will die due to liver cancer in the U.S.2,3
Worldwide, nearly 800,000 new cases are diagnosed annually, and the
disease accounts for more than 700,000 deaths each year.4
About CABOMETYX® (cabozantinib)
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 RCC who have received prior anti-angiogenic
therapy. In February of 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. This agreement was amended in December of 2016 to
include commercialization rights for Ipsen in Canada. On September 9,
2016, the European Commission approved CABOMETYX tablets for the
treatment of advanced RCC in adults who have received prior vascular
endothelial growth factor (VEGF)-targeted therapy in the European Union,
Norway and Iceland.
On January 30, 2017, Exelixis and Takeda Pharmaceutical Company Limited
announced an exclusive licensing agreement for the commercialization and
further clinical development of cabozantinib for all future indications
in Japan, including RCC.
CABOMETYX is not indicated for the treatment of advanced HCC.
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 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
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
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
Please see full Prescribing Information at 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 lead compounds, cabozantinib and
cobimetinib, and advanced them into clinical development before entering
into partnerships with leading biopharmaceutical companies in our
efforts to bring them to patients globally. With growing revenues from
the three resulting commercialized products – CABOMETYX®,
COMETRIQ®, and COTELLIC® – we are reinvesting in
our business to maximize the potential of our pipeline, which we intend
to supplement 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. For more information
about Exelixis, please visit www.exelixis.com
or follow @ExelixisInc on Twitter.
Forward-Looking Statement Disclaimer
This press release
contains forward-looking statements, including, without limitation,
statements related to: Exelixis’ plans to submit an sNDA to the FDA in
the first quarter of 2018 for the treatment of patients with advanced
HCC; Exelixis’ plan to submit the detailed results from CELESTIAL for
presentation at a future medical conference; the therapeutic potential
of cabozantinib as a treatment for patients with advanced liver cancer;
Exelixis’ commitment to studying cabozantinib in a range of tumor types
as part of the company’s mission to deliver medicines that improve
treatment outcomes and give patients hope for the future; Exelixis’ plan
to discuss the trial results with regulatory authorities and determine
next steps for the trial, including offering patients currently
receiving placebo the opportunity to cross over to the cabozantinib arm;
growing revenues from CABOMETYX, COMETRIQ, and COTELLIC 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; and Exelixis’ mission to deliver
the next generation of Exelixis medicines and help patients recover
stronger and live longer. Words such as “plans,” “will,” “potential,”
“committed,” “mission,” “next steps,” 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: risks and uncertainties related to regulatory review and
approval processes and Exelixis’ compliance with applicable legal and
regulatory requirements; the availability of data at the referenced
time; 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 relationships with its
cabozantinib collaboration partners, including, the level of their
investment in the resources necessary to successfully commercialize
cabozantinib in the territories where it is approved; market acceptance
of CABOMETYX, COMETRIQ, and COTELLIC and the availability of coverage
and reimbursement for these products; the risk that unanticipated
developments could adversely affect the commercialization of CABOMETYX,
COMETRIQ, and COTELLIC; the level of costs associated with Exelixis’
commercialization, research and development and other activities;
Exelixis’ dependence on its relationship with Genentech/Roche with
respect to cobimetinib and Exelixis’ ability to maintain its rights
under the collaboration; 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 August 2, 2017, 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
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
1. Hepatocellular Carcinoma – United States, 2001-2006. Morbidity and
Mortality Weekly Report. Centers for Disease Control and Prevention.
Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5917a3.htm.
Accessed October 2017.
2. American Cancer Society: Cancer Facts and
Figures 2017. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf.
Accessed October 2017.
3. Weledji E, Orock G, Ngowe M, NsaghaD. How
grim is hepatocellular carcinoma? Annals of Medicine and Surgery.
4. Estimated cancer incidence, mortality and
prevalence worldwide. International Agency for Research on Cancer,
GLOBOCAN 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
Accessed October 2017.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171016005409/en/
Source: Exelixis, Inc.
EVP, Public Affairs and Investor Relations
Director, Public Affairs and Advocacy