|[July 16, 2014]
New England Journal of Medicine Publishes Ipsen's Somatuline® CLARINET® Phase III Results in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors
BASKING RIDGE, N.J. --(Business Wire)--
The U.S. affiliate of Ipsen (Euronext: IPN; ADR: IPSEY) today announced
that the New England Journal of Medicine has published clinical trial
results showing that Somatuline® Autogel® /
Somatuline® Depot® (lanreotide) Injection 120 mg
(referred to as Somatuline®) achieved statistically
significant prolongation of progression free survival (PFS) over placebo
in patients with metastatic gastroenteropancreatic neuroendocrine tumors
(GEP-NETs). CLARINET®, an investigational Phase III
randomized, double-blind, placebo-controlled study of the
antiproliferative effects of Somatuline® was conducted in 48
centers across 14 countries. The article titled "Lanreotide in
Metastatic Enteropancreatic Neuroendocrine Tumors" is available online
at NEJM.org and has been published in the July 17th edition (N. Engl. J.
Med. 2014; 371: 224-233).
The data gathered from 204 GEP-NET (News - Alert) patients over the 96-week study
showed that placebo-treated patients had a median PFS of 18.0 months and
33.0% had not progressed or died at 96 weeks, whereas the median PFS for
Somatuline® treated patients was not reached and 65.1% had
not progressed or died at 96 weeks (stratified logrank test, p<0.001).
This represented a 53% reduction in risk of disease progression or death
based on a hazard ratio of 0.47 (95% CI: 0.30-0.73). These statistically
and clinically significant antiproliferative effects of Somatuline®
were observed in a large population of patients with grade G1 or G2 (News - Alert)
(World Health Organization classification) GEP-NETs, and independent of
hepatic tumor volume (=25% or >25%). Quality of life measures were not
different between the Somatuline® and placebo groups. Safety
data generated from the study are consistent with the known safety
profile of Somatuline®.
"The CLARINET® data are compelling, since no
similar GEP-NET progression free survival data exist for a somatostatin
analog in such a large, multinational study population," said Dr.
Martyn Caplin, Professor of Gastroenterology & Gastrointestinal
Neuroendocrinology, Royal Free Hospital (London, UK) and lead author and
principal investigator of the CLARINET® study.
"The peer-reviewed publication of CLARINET®
results in the New England Journal of Medicine highlights the robust
data that showed an antiproliferative effect of Somatuline®
in the treatment of GEP-NETs," said Claude Bertrand, Executive Vice
President R&D and Chief Scientific Officer. "Based on these
significant results, Ipsen has initiated a worldwide registration
program and on July 1st 2014, the submission of a Supplemental New Drug
Application for Somatuline® for the treatment
of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to the U.S.
FDA as well as Marketing Authorization variations in 25 countries of the
European Union were announced."
"This is potentially exciting news for physicians treating GEP-NETs,
as the data showed anti-tumor activity and a delay in
disease-progression in patients treated with Somatuline®
Depot®," said Dr. Alexandria Phan, CLARINET
investigator, Director of GI Medical Oncology at Houston Methodist
The data from CLARINET® is considered investigational, as
Somatuline® is not indicated for anti-proliferative treatment
of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in any
market. Somatuline® is approved for treatment of symptoms
associated with neuroendocrine tumors, which can include the treatment
of GEP-NET patients experiencing symptoms from carcinoid syndrome, in
many markets where it is marketed as Somatuline® Autogel®.
Somatuline® is not approved in the U.S. to treat GEP-NETs or
the symptoms thereof, where it is marketed as Somatuline®
Depot® for acromegaly.
CLARINET® is a randomized, double-blind, placebo-controlled
study of lanreotide's antiproliferative response in patients with
enteropancreatic neuroendocrine tumors (ClinicalTrials.gov NCT00353496).
This 96-week multinational study was conducted in collaboration with UK
& Ireland Neuroendocrine Tumour Society (UKI NETS) and the European
Neuroendocrine Tumour Society (ENETS).
A total of 204 patients from 48 centers across 14 countries with well or
moderately differentiated non-functioning enteropancreatic
neuroendocrine tumors and a proliferation index (Ki67) of <10%, were
randomized to treatment with Somatuline® Autogel®
120 mg (n=101) or placebo (n=103). At enrollment, primary tumor
locations were pancreas (44%), midgut (36%), hindgut (7%) and unknown
(13%). Most patients had stable disease (96%) and were treatment-naïve
(84%). Thirty percent of patients had a Ki67 of 3%-=10% (WHO grade 2)
and 33% had an hepatic tumor load >25%.
The primary efficacy endpoint was time to either disease progression
(centrally assessed using Response Evaluation Criteria In Solid Tumors,
RECIST 1.0) or death. Two baseline computed tomography or magnetic
resonance imaging scans were performed (the second one done 12 to 24
weeks after the first imaging test), followed by additional scans at
12-week intervals during the first year and 24-week intervals during the
second year up to 96 weeks.
Safety data generated from the CLARINET® study were
consistent with the known safety profile of Somatuline®.
Similar proportions of each treatment group experienced adverse events
(lanreotide, 88; placebo, 90%). Most of these patients experienced mild
(17% per group) or moderate events (lanreotide, 44%; placebo, 43%).
One-half of the lanreotide group experienced treatment-related adverse
events (vs. 28% with placebo), most commonly diarrhea (26% vs. 9%,
respectively), followed by abdominal pain and cholelithiasis. Six
patients experienced adverse events leading to withdrawal, three in each
group, with only one considered by the investigator to be
treatment-related in the Somatuline® group. Fifty-seven
patients experienced 122 serious adverse events; eight were considered
treatment-related (lanreotide, seven events; placebo, one event).
About gastroenteropancreatic neuroendocrine tumors
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are serious rare
types of cancer. They constitute a heterogeneous group of tumors most
often arising from cells in the gastrointestinal tract or the pancreas;
although rare, their incidence has been on the rise (4-6 fold increase
in the last 30 years). They have the ability to secrete functional
amines and peptides and based on the type and amount of these bioactive
substances in circulation, they can or cannot result in an identifiable
hormonal clinical syndrome. GEP-NETs can be clinically silent for long
periods of time, delaying the diagnosis until late presentation with
hormonal related symptoms or with symptoms related to tumor mass effect
such as intestinal obstruction or abdominal pain.
About Somatuline® Depot®
in the United States
In the United States, Somatuline® Depot® is
indicated for the long-term treatment of patients with acromegaly who
have had an inadequate response to or cannot be treated with surgery
Somatuline® Depot® is not indicated for the
treatment of GEP-NETs.
The active substance in Somatuline® Depot®
is lanreotide acetate, a somatostatin analogue that inhibits the
secretion of several endocrine, exocrine and paracrine functions.
Select Important Safety Information about Somatuline®
Depot for Patients
Somatuline Depot may cause serious side effects including:
Changes in your blood sugar (high blood sugar or low blood sugar)
Slow heart rate
High blood pressure
The most common side effects of Somatuline Depot include diarrhea,
gallstones, stomach area (abdominal) pain, nausea, and pain, itching, or
a lump at the injection site.
These are not all the possible side effects of Somatuline Depot. Tell
your doctor if you have any side effect that bothers you or that does
not go away.
Before you receive Somatuline Depot, talk to your doctor about:
All of your medical conditions, including:
Gallbladder, thyroid, heart, kidney, or liver problems
Allergy to latex or natural dry rubber
Pregnancy or plans to become pregnant
It is not known if Somatuline Depot could harm your unborn baby
Breast-feeding or plans to breast-feed
It is not known if Somatuline Depot passes into breast milk
Any medicines (prescription and nonprescription) you are taking,
Insulin or other diabetes medicines
A cyclosporine (such as Gengraf™, Neoral®, or Sandimmune®)
A medicine called bromocriptine (such as Parlodel®)
Medicines that lower your heart rate (such as beta blockers)
While on Somatuline Depot:
Tell your doctor if you have sudden pain in your upper right stomach
(abdominal) area or in your right shoulder or between your shoulder
blades, or if you have yellowing of your skin and whites of your eyes,
fever with chills, or nausea as these could be symptoms related to
If you have diabetes, test your blood sugar as your doctor tells you
to. Your doctor may change your dose of diabetes medicine especially
when you first start receiving Somatuline Depot or if your dose of
Somatuline Depot changes.
Before each treatment, read the Patient Information that comes with
each Somatuline Depot package as there may be new information. Talk
with your doctor about your medical condition or your treatment. Your
doctor is your primary source of information about treatment.
Please see the Patient Information for Somatuline Depot at http://somatulinedepot.com/assets/files/fpo_patient_pi.pdf
Select Important Safety Information about Somatuline® Depot for
Somatuline is contraindicated in patients with hypersensitivity to
lanreotide or related peptides.
Warnings and Precautions
Somatuline may reduce gallbladder motility and lead to gallstone
formation. Periodic monitoring may be needed
Patients may experience hypoglycemia or hyperglycemia. Glucose level
monitoring is recommended and antidiabetic treatment adjusted
Somatuline may decrease heart rate. In cardiac studies, the most
common cardiac adverse reactions were sinus bradycardia, bradycardia,
and hypertension. Dose adjustment of coadministered drugs that
decrease heart rate may be necessary
Somatuline may decrease bioavailability of cyclosporine. Cyclosporine
dose may need to be adjusted
The most common adverse reactions (incidence >5%) were diarrhea (37%),
cholelithiasis (20%), abdominal pain (19%), nausea (11%), injection-site
reaction (9%), constipation (8%), flatulence (7%), headache (7%),
arthralgia (7%), vomiting (7%), and loose stools (6%).
Use in Special Populations
Patients with moderate and severe renal impairment or moderate and
severe hepatic impairment: Initial dose is 60 mg every 4 weeks.
Please see the full Prescribing Information for Somatuline Depot at http://somatulinedepot.com/pdf/pi_2013november.pdf
Ipsen is a global specialty-driven pharmaceutical company with total
sales exceeding €1.2 billion in 2013. Ipsen's ambition is to become a
leader in specialty healthcare solutions for targeted debilitating
diseases. Its development strategy is supported by 3 franchises:
neurology, endocrinology and urology-oncology. 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. In 2013, R&D expenditure totaled close to €260 million,
representing more than 21% of Group sales. Ipsen also has a significant
presence in primary care. The Group has close to 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.
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are based on the Group's management strategy, current views and
assumptions. Such statements involve known and unknown risks and
uncertainties that may cause actual results, performance or events to
differ materially from those anticipated herein. All of the above risks
could affect the Group's future ability to achieve its financial
targets, which were set assuming reasonable macroeconomic conditions
based on the information available today.
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including the Group's expectations regarding future events, including
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in this document were prepared without taking into account external
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