Regulatory News:
Ipsen (Euronext:IPN; ADR: IPSEY) today announced that Somatuline®
Depot® (lanreotide) Injection 120 mg (referred to as
Somatuline®) was approved by the U.S. Food and Drug
Administration (FDA) for the treatment of adult patients with
unresectable, well- or moderately-differentiated, locally advanced or
metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Marc de Garidel, Chairman and Chief Executive Officer of Ipsen
stated: “I am pleased with the approval by the FDA of this new
indication for Somatuline®, which is a
testimony to the scientific quality of those clinical results. Ipsen is
now prepared to launch in the US the first antitumor therapeutic
approved for the treatment of both pancreatic and gastrointestinal
neuroendocrine tumors. This represents a significant step forward in the
treatment of this cancer, which affects thousands of Americans. In the
US, we have diligently built a robust commercial organization that will
execute on the launch of Somatuline® in this
indication in early 2015.” Marc de Garidel concluded:
“Today marks a major strategic milestone in our history, as we are now
in a position to fully leverage our presence in the US.”
Pr Martyn Caplin, Professor of Gastroenterology & Gastrointestinal
Neuroendocrinology, Royal Free Hospital (London, UK) and Principal
Investigator of CLARINET®, commented: “Somatuline®
has shown substantial clinical benefit in treating both pancreatic and
gastrointestinal neuroendocrine tumors and can be considered as a first
line therapy in the treatment of those tumors. This rapid approval from
the FDA is welcome news for NET patients, their families and the whole
NET community. I am looking forward to further regulatory approvals
around the world so that patients with pancreatic and gastrointestinal
neuroendocrine tumors can have access to this effective and well
tolerated therapy.”
Somatuline® was previously approved in the United States for
the long-term treatment of acromegalic patients who have had an
inadequate response to surgery and/or radiotherapy, or for whom surgery
and/or radiotherapy is not an option.
Somatuline®’s approval was based on demonstration of improved
progression-free survival (PFS) in CLARINET® multi-center,
international, randomized (1:1), double-blind, placebo-controlled study
that enrolled 204 patients with unresectable, well- or
moderately-differentiated, locally advanced or metastatic,
non-functioning GEP-NETs. Patients were randomized to receive either
Somatuline® (lanreotide) 120 mg or placebo subcutaneously
every 28 days. The primary efficacy endpoint was PFS as determined by
independent central radiology review. The trial demonstrated a
significant prolongation of PFS for the Somatuline® (lanreotide)
arm [HR 0.47 (95% CI: 0.30, 0.73); p < 0.001; stratified log-rank test].
The median PFS in the Somatuline® (lanreotide) arm had not
been reached at the time of the final analysis and therefore is greater
than 22 months. The median PFS in the placebo arm was 16.6 months.
Safety data were evaluated in 101 patients who received at least one
dose of Somatuline® (lanreotide). The most commonly (greater
than or equal to 10%) reported adverse reactions in Somatuline® (lanreotide)-treated
patients were abdominal pain, musculoskeletal pain, vomiting, headache,
injection site reaction, hyperglycemia, hypertension, and
cholelithiasis. The most common serious adverse reaction of Somatuline®
(lanreotide) observed in this trial was vomiting (4%).
The recommended dose and schedule for Somatuline® (lanreotide)
for GEP-NET is lanreotide 120 mg administered by deep subcutaneous
injection every 28 days. Treatment should continue until disease
progression or unacceptable toxicity.
About Pancreatic and Gastrointestinal Neuroendocrine Tumors
Pancreatic and gastrointestinal neuroendocrine tumors are rare cancers.
There are an estimated 112,000 individuals1;2 currently
living with pancreatic and gastrointestinal neuroendocrine tumors in the
U.S., and the incidence and prevalence of this type of cancer have risen
4-to-6 fold in the last 30 years3. Furthermore, up to ninety
percent of patients are diagnosed at a late stage.4
About CLARINET®
CLARINET® was an Phase III, 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 the UK & Ireland Neuroendocrine Tumour Society (UKI
NETS) and the European Neuroendocrine Tumour Society (ENETS). CLARINET®
results were published in the July 17th, 2014 issue of
The New England Journal of Medicine5.
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® 120 mg every 4 weeks
(n=101) or placebo (n=103). At enrollment, primary tumor locations were
pancreas (45%), midgut (36%), hindgut (7%) and unknown (13%). Thirty
percent of patients had a Ki67 of 3% to 10% (WHO grade 2) and 33% had a
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 scans were
performed, followed by additional scans (tomography or magnetic
resonance imaging) at 12- week intervals during the first year and
24-week intervals during the second year of study up to week 96.
The data showed that placebo-treated patients had a median PFS of 16.6
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 antitumoral
effects of Somatuline® were observed in a large population of
patients with grade G1 or G2 (Ki-67 < 10%; World Health Organization
2010 classification) GEP-NETs. Overall survival and 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®. Most common adverse
reactions (>10%) are abdominal pain (34%), musculoskeletal pain (19%),
vomiting (19%), headache (16%), injection site reaction (15%),
hyperglycemia (14%), hypertension (14%), cholelithiasis (14%). The rates
of discontinuation due to treatment-related adverse reactions were 5%
(5/101 patients) in the Somatuline® 120mg arm and 3% (3/103
patients) in the placebo arm.
About Somatuline®
The active substance in Somatuline® is lanreotide acetate, a
somatostatin analogue 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
authorization for the treatment of acromegaly or the symptomatic
treatment of neuroendocrine tumors.
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® will be delivered via a newly approved in the US,
ready-to-use, prefilled syringe which incorporates Safe’n’Sound®6
technology, including a retractable guard to help avoid accidental
needle sticks, and it is manufactured without latex or natural dry
rubber. The new delivery device does not require reconstitution and is a
low volume (0.5 mL) deep subcutaneous injection offering a streamlined
process that supports full dose delivery.
Adverse Reactions
In the GEP-NET pivotal trial, the most common adverse reactions
(incidence >10% and more common than placebo) in patients treated with
Somatuline® vs placebo were abdominal pain (34% vs 24%),
musculoskeletal pain (19% vs 13%), vomiting (19% vs 9%), headache (16%
vs 11%), injection site reaction (15% vs 7%), hyperglycemia (14% vs 5%),
hypertension (14% vs 5%), and cholelithiasis (14% vs 7%).
The product information should be consulted for a complete list of
undesirable effects, warnings and precautions and contraindications for
use.
About Ipsen
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 uro-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. Moreover, 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.
Ipsen Forward Looking Statements
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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
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targets, which were set assuming reasonable macroeconomic conditions
based on the information available today. Use of the words "believes,"
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in the future, and not exclusively on historical data. Actual results
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obtained during pre-clinical trials will be confirmed subsequently
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1 Öberg, K, Knigge, U, Kwekkeboom, D, Perren, A, (2012).
Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up. Annals of
Oncology, 23(Supplement 7), 124-130
2 United States
Census Bureau. Census Website. http://www.census.gov/popclock/.
Accessed December 10, 2014.
3 Lawrence B, Gustafsson BI,
Chan A, Svejda B, Kidd M, Modlin IM (2011). The epidemiology of
gastroenteropancreatic neuroendocrine tumors. Endocrinology and
Metabolism Clinics of North America, 40(1), 1-18, vii Yao JC, Hassan M,
Phan AT, et al. (2008) One hundred years after "carcinoid": epidemiology
of and prognostic factors for neuroendocrine tumors in 35,825 cases in
the United States. Journal of Clinical Oncology,; 26(18), 3063-3072
4
Center for Carcinoid and Neuroendocrine Tumors. Mount Sinai Hospital
Website: http://www.mountsinai.org/patient-care/service-areas/digestive-disease/areas-of-care/neuroendocrine-tumors.
Accessed October 14, 2014
5 “Lanreotide in Metastatic
Enteropancreatic Neuroendocrine Tumors”, July 17th 2014 edition, N.
Engl. J. Med. 2014; 371: 224-233
6 Safe’n’Sound is a
registered trademark of Nemera La Verpillière SAS
Copyright Business Wire 2014