– 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 –
Exelixis, 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.
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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 of cabozantinib.
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, 2018.
“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
longer.”
“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 ≤ 0.021).
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.
About HCC
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 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 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.
About Ipsen
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.
References1 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.
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Exelixis, Inc.Investors:Susan Hubbard,
650-837-8194EVP, Public Affairs and Investor
Relationsshubbard@exelixis.comorMedia:Lindsay Treadway,
650-837-7522Director, Public Affairs and Advocacy
Relationsltreadway@exelixis.com
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