– Pivotal phase 3 CELESTIAL trial results, including additional
subset analyses, to be presented during oral session on Friday, January
19 at the 2018 American Society of Clinical Oncology’s Gastrointestinal
Cancers Symposium (ASCO-GI) –
– Exelixis to submit supplemental New Drug Application to U.S.
Food and Drug Administration (FDA) in the first quarter of 2018 –
SOUTH SAN FRANCISCO, Calif. & PARIS--(BUSINESS WIRE)--Jan. 16, 2018--
Inc. (NASDAQ:EXEL) and Ipsen (Euronext:IPN; ADR:IPSEY) today
announced detailed results of the pivotal phase 3 CELESTIAL trial in
patients with previously treated advanced hepatocellular carcinoma
(HCC), which will be presented in a late-breaking oral session at the
2018 ASCO-GI Symposium being held in San Francisco, January 18-20, 2018.
In CELESTIAL, cabozantinib provided a statistically significant and
clinically meaningful improvement versus placebo in overall survival
(OS), the trial’s primary endpoint, at the planned second interim
analysis (pre-specified critical p-value ≤ 0.021) for the population of
second- and third-line patients enrolled in this study. Median OS was
10.2 months with cabozantinib versus 8.0 months with placebo (HR 0.76,
95 percent CI 0.63-0.92; p=0.0049). Median progression-free survival
(PFS) was more than doubled, at 5.2 months with cabozantinib and 1.9
months with placebo (HR 0.44, 95 percent CI 0.36-0.52; p<0.0001).
Objective response rates per RECIST 1.1 were 4 percent with cabozantinib
and 0.4 percent with placebo (p=0.0086). Disease control (partial
response or stable disease) was achieved by 64 percent of the
cabozantinib group compared with 33 percent of the placebo group.
This press release features multimedia. View the full release here:
In a subgroup analysis of patients whose only prior therapy for advanced
HCC was sorafenib (70 percent of patients in the study), median OS was
11.3 months with cabozantinib versus 7.2 months with placebo (HR 0.70,
95 percent CI 0.55-0.88). Median PFS in the subgroup was 5.5 months with
cabozantinib versus 1.9 months with placebo (HR 0.40, 95 percent CI
0.32-0.50). Adverse events were consistent with the known safety profile
Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center, New
York and lead investigator on CELESTIAL, will present detailed findings,
including analyses of OS and PFS in various patient subgroups, during
Oral Abstract Session B: Cancers of the Pancreas, Small Bowel, and
Hepatobiliary Tract, which begins at 2:15 p.m. PT on Friday, January 19,
“Patients with advanced hepatocellular carcinoma often have a poor
prognosis and limited treatment options following prior systemic
therapy,” said Dr. Abou-Alfa. “The clinically significant benefits in
both overall survival and progression-free survival shown in the
CELESTIAL trial suggest that, if approved, cabozantinib could become an
important addition to the treatment landscape for these patients.”
“We are excited by the potential benefit cabozantinib may offer to
patients with previously treated advanced hepatocellular carcinoma,”
said Gisela Schwab, M.D., President, Product Development and Medical
Affairs and Chief Medical Officer, Exelixis. “Given the worldwide
prevalence of advanced hepatocellular carcinoma, there is a continued
urgency to bring new treatment options to this patient population. We
look forward to submitting our supplemental New Drug Application to the
FDA for cabozantinib in the first quarter of 2018, and to further
advancing our mission to help cancer patients recover stronger and live
“Patients diagnosed with advanced hepatocellular carcinoma urgently need
new treatment options,” said Alexandre Lebeaut, M.D., Executive
Vice-President, R&D, Chief Scientific Officer, Ipsen. “The positive
results of the pivotal phase 3 CELESTIAL trial are encouraging for both
physicians and patients, and we have committed to file in the first half
of 2018 a variation of the initial application to the EMA and other
relevant regulatory agencies.”
The most common (≥10 percent) grade 3 or 4 adverse events in the
cabozantinib group compared to the placebo group were palmar-plantar
erythrodysesthesia (17 percent vs. 0 percent), hypertension (16 percent
vs. 2 percent), increased aspartate aminotransferase (12 percent vs. 7
percent), fatigue (10 percent vs. 4 percent), and diarrhea (10 percent
vs. 2 percent). Treatment-related grade 5 adverse events occurred in six
patients in the cabozantinib group (hepatic failure, esophagobronchial
fistula, portal vein thrombosis, upper gastrointestinal hemorrhage,
pulmonary embolism and hepatorenal syndrome) and in one patient in the
placebo group (hepatic failure). Sixteen percent of patients in the
cabozantinib arm and three percent of patients in the placebo arm
discontinued treatment due to treatment-related adverse events.
Webcast for the Financial Community
Exelixis and its partner Ipsen will jointly host a live webcast on
Friday, January 19. The webcast will begin at 6:30 p.m. PT / 9:30 p.m.
ET. During the webcast, Exelixis and Ipsen management and an invited
guest speaker will review results from the CELESTIAL trial.
To access the webcast link, log onto www.exelixis.com
and proceed to the News & Events / Event Calendar page under the
Investors & Media heading. Please connect to the company’s website at
least 15 minutes prior to the webcast to ensure adequate time for any
software download that may be required to view the program. To listen to
an audio-only version of the program by phone, please dial 855-793-2457
(domestic) or 631-485-4921 (international/toll dial) and use passcode
2478857. A telephone replay will be available until 11:59 p.m. ET on
January 26, 2018. Access numbers for the telephone replay are:
855-859-2056 (domestic) and 404-537-3406 (international); the passcode
is 2478857. A webcast replay will also be available archived on www.exelixis.com
for one year.
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.
Based on available clinical trial data from various published trials
conducted in the second-line setting of advanced HCC, the CELESTIAL
trial design 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 approximately 50 percent
and 75 percent of the planned 621 events. At the first interim analysis
conducted by the independent data monitoring committee the observed
hazard ratio was 0.71 and the p-value was 0.0041, which did not cross
the stopping boundary for the first interim analysis (p ≤ 0.0037).
On October 16, 2017, Exelixis announced that the independent data
monitoring committee recommended that the trial be stopped for efficacy
following review of the second planned interim analysis, as the trial
had met its primary endpoint of OS (pre-specified critical p-value ≤
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.
Liver cancer is the second-leading cause of cancer death worldwide,
accounting for more than 700,000 deaths and nearly 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 nearly
42,000 new cases in the U.S. in 2018.2 HCC is the
fastest-rising cause of cancer-related death in U.S.3 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 and Switzerland for the treatment of
advanced RCC in adults who have received prior vascular endothelial
growth factor (VEGF)-targeted therapy. Ipsen also submitted to European
Medicines Agency (EMA) the regulatory dossier for cabozantinib as a
treatment for first-line advanced RCC in the European Union on August
28, 2017; on September 8, 2017, Ipsen announced that the EMA validated
the application. 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, 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 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 lead
compounds, cabozantinib and cobimetinib, and advanced them into clinical
development before entering into partnerships with leading
biopharmaceutical companies in our efforts to bring these medicines to
patients globally. We are steadfast in our commitment to prudently
reinvest in our business to maximize the potential of our pipeline. We
intend to supplement 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 recently earned a spot on
Deloitte’s Technology Fast 500 list, a yearly award program honoring the
500 fastest-growing companies over the past four years. For more
information about Exelixis, please visit www.exelixis.com
or follow @ExelixisInc on Twitter.
Ipsen is a global specialty-driven pharmaceutical group with total sales
exceeding €1.4 billion in 2015. Ipsen sells more than 20 drugs in more
than 115 countries, with a direct commercial presence in more than 30
countries. Ipsen’s ambition is to become a leader in specialty
healthcare solutions for targeted debilitating diseases. Its fields of
expertise cover oncology, neurosciences and endocrinology (adult &
pediatric). Ipsen’s commitment to oncology is exemplified through its
growing portfolio of key therapies improving the care of patients
suffering from prostate cancer, bladder cancer and neuro-endocrine
tumors. Ipsen also has a significant presence in primary care. Moreover,
the Group has an active policy of partnerships. Ipsen's R&D is focused
on its innovative and differentiated technological platforms, peptides
and toxins, located in the heart of the leading biotechnological and
life sciences hubs (Les Ulis/Paris-Saclay, France; Slough/Oxford, UK;
Cambridge, US). In 2015, R&D expenditure totaled close to €193 million.
The Group has more than 4,600 employees worldwide. Ipsen’s shares are
traded on segment A of Euronext Paris (stock code: IPN, ISIN code:
FR0010259150) and eligible to the “Service de Règlement Différé”
(“SRD”). The Group is part of the SBF 120 index. Ipsen has implemented a
Sponsored Level I American Depositary Receipt (ADR) program, which trade
on the over-the-counter market in the United States under the symbol
IPSEY. For more information on Ipsen, visit www.ipsen.com.
Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: Exelixis’ plan to submit a
supplemental New Drug Application to the FDA in the first quarter of
2018; the plan to present detailed findings from CELESTIAL at the 2018
ASCO-GI Symposium; the clinical and therapeutic potential of
cabozantinib for patients with previously treated advanced HCC; Ipsen’s
plan to file a variation of the initial application to the EMA and other
relevant regulatory agencies in the first half of 2018; Exelixis’ plan
to advance its mission to deliver medicines that improve treatment
outcomes; and Exelixis’ commitment to reinvesting in its business to
maximize the potential of its pipeline, including supplementing its
existing therapeutic assets through targeted business development
activities and internal drug discovery. Words such as “will,” “could,”
“potential,” “look forward,” “mission,” “commitment,” “intend,” 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; the level of costs associated with Exelixis’
commercialization, research and development and other activities;
competition in the area of business development activities and the
inherent uncertainty of the drug discovery process; 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; Exelixis’ dependence on its relationship with Genentech/Roche
with respect to cobimetinib and Exelixis’ ability to maintain its rights
under the collaboration; market acceptance of CABOMETYX, COMETRIQ, and
COTELLIC and the availability of coverage and reimbursement for these
products; Exelixis’ dependence on third-party vendors for the
development, manufacture and supply of its products; 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 November 1, 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 based.
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
1 Cancer Incidence and Mortality Worldwide.
Liver Cancer. International Agency for Research on Cancer, GLOBOCAN
2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
Accessed January 2018.
2 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 January 2018.
3 Mittal S, El-Serag HB.
Epidemiology of HCC: Consider the Population. Journal of Clinical
Gastroenterology. 2013. 47:S2-S6.
4 Weledji E, Orock
G, Ngowe M, NsaghaD. How grim is hepatocellular carcinoma? Annals of
Medicine and Surgery. 2014. 3:71-76.
View source version on businesswire.com: http://www.businesswire.com/news/home/20180116006839/en/
Source: Exelixis, Inc.
EVP, Public Affairs and Investor
Director, Public Affairs and Advocacy