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 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 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
(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 Pr
Martyn Caplin, Professor of Gastroenterology & Gastrointestinal
Neuroendocrinology, Royal Free Hospital (London, UK) and lead
author and principal investigator of the CLARINET®
"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."
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 US 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 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
neuroedocrine 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.
The active substance in Somatuline® is lanreotide acetate, a
somatostatin analog that inhibits the secretion of several endocrine,
exocrine and paracrine functions. It has been shown to be effective in
inhibiting the secretion of GH and certain hormones secreted by the
digestive system. Somatuline® is marketed as Somatuline®
Depot® within the United States and as Somatuline®
Autogel® in other countries where it has marketing
Somatuline® was initially developed and continues to be used
for the treatment of acromegaly in many countries, including the United
States, where it is indicated for the long-term treatment of patients
with acromegaly who have had an inadequate response to or cannot be
treated with surgery and/or radiotherapy. Somatuline® is not
currently indicated as an antiproliferative agent for the treatment of
GEP-NETs. Somatuline® is approved for the treatment of
symptoms associated with neuroendocrine tumors in many markets, but is
not approved within the United States for this indication.
Important Safety Information about Somatuline®
The most commonly reported adverse drug reactions following treatment
with lanreotide are gastrointestinal disorders and cholelithiasis. In
addition there have been reports of changes to glucose regulation,
levels of liver enzymes, changes to heart rate, injection site and
allergic reactions. The product information should be consulted for a
complete list of undesirable effects, warnings and precautions and
contraindications for use.
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.
Forward Looking Statement
The forward-looking statements, objectives and targets contained herein
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.
Moreover, the targets described in this document were prepared without
taking into account external growth assumptions and potential future
acquisitions, which may alter these parameters. These objectives are
based on data and assumptions regarded as reasonable by the Group. These
targets depend on conditions or facts likely to happen in the future,
and not exclusively on historical data. Actual results may depart
significantly from these targets given the occurrence of certain risks
and uncertainties, notably the fact that a promising product in early
development phase or clinical trial may end up never being launched on
the market or reaching its commercial targets, notably for regulatory or
competition reasons. The Group must face or might face competition from
Generics that might translate into a loss of market share.
Furthermore, the Research and Development process involves several
stages each of which involves the substantial risk that the Group may
fail to achieve its objectives and be forced to abandon its efforts with
regards to a product in which it has invested significant sums.
Therefore, the Group cannot be certain that favorable results obtained
during pre-clinical trials will be confirmed subsequently during
clinical trials, or that the results of clinical trials will be
sufficient to demonstrate the safe and effective nature of the product
concerned. The Group also depends on third parties to develop and market
some of its products which could potentially generate substantial
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damage to the Group's activities and financial results. The Group cannot
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situations could have a negative impact on the Group's business,
financial position or performance.
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revise any forward looking statements, targets or estimates contained in
this press release to reflect any change in events, conditions,
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