-
Constella® (linaclotide) is the first and
only medicine approved by the European Commission for the symptomatic
treatment of moderate to severe IBS-C in adults, that improves
abdominal pain/discomfort, bloating and constipation
-
First launches in Europe are expected in the first half of 2013
-
IBS-C is a functional gastrointestinal disorder affecting
approximately 15 million adults across the European Union1
BARCELONA, Spain & CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Almirall, S.A. (ALM:MC) and Ironwood Pharmaceuticals, Inc. (NASDAQ:
IRWD) announced today that the European Commission has granted marketing
authorization to Constella® (linaclotide 290mcg) for the
symptomatic treatment of moderate to severe Irritable Bowel Syndrome
with Constipation (IBS-C) in adults. This approval follows the positive
recommendation received from the European Committee for Medicinal
Products for Human Use (CHMP) in September.
Constella® is an oral, once-daily medication. Linaclotide,
the active ingredient in Constella®, is a guanylate cyclase-C
agonist (GCCA) with visceral analgesic and secretory activities, as
stated in the product label for European use. In non-clinical studies,
linaclotide has been shown to reduce visceral pain by decreasing
pain-fiber activity and to accelerate gastrointestinal transit by
increasing intestinal fluid secretion. Linaclotide acts locally in the
intestine with minimal systemic exposure.
"Despite affecting more than 10% of the population in the EU there
are few effective treatment options for IBS. Approximately one third of
IBS patients suffer from the IBS-C form of the disease and the approval
of Constella® provides physicians with an
innovative medication, for improving the lives of patients whose quality
of life is impaired," said Professor Jan Tack, Head of Clinic in the
Department of Gastroenterology, and Professor in Internal Medicine at
the University Hospital Gasthuisberg of the University of Leuven,
Belgium.
IBS is a functional gastrointestinal disorder impacting over 10% of the
European population, and it is estimated that one-third of IBS patients
suffer from IBS-C1, which means that approximately 15 million
adults across the European Union might be affected. Symptoms associated
with IBS-C include abdominal pain and discomfort, bloating, and
constipation resulting in a significant impact on affected individuals.
There are few prescription treatment options for this condition approved
in the European Union. Constella® is the first and only
prescription medicine approved by the European Commission for the
symptomatic treatment of moderate to severe Irritable Bowel Syndrome
with Constipation (IBS-C) in adults.
"Almirall is delighted with the approval of Constella®,
the first prescription medicine approved by the European Commission for
the treatment of IBS-C in adults. This new medicine has the potential to
improve some of the hallmark symptoms of IBS-C patients who up until now
have had few treatment options. Furthermore the approval of Constella®
is an important growth opportunity for Almirall and will strengthen our
gastrointestinal franchise," said Eduardo Sanchiz, Chief Executive
Officer at Almirall.
Almirall expects to begin launching Constella® in Europe in
the first half of 2013.
"Linaclotide was discovered by Ironwood scientists, and obtaining
marketing authorization for Constella® in Europe is
important progress towards our goal of translating knowledge into
medicines that make a difference for patients," said Peter Hecht,
Ironwood's Chief Executive Officer. "We look forward to continuing to
work closely with our partner Almirall in their efforts to bring
Constella® to adult IBS-C patients in Europe, and we
will continue collaborating with our global network of partners with the
goal of bringing this medicine to appropriate patients worldwide."
In April 2009, Almirall signed a license agreement with Ironwood, under
which Almirall holds exclusive marketing rights for linaclotide in all
European Union member states, plus Russia, the CIS (Commonwealth of
Independent States of the former USSR), Switzerland, Norway and Turkey,
as well as other countries in Europe, including the countries of former
Yugoslavia. In September 2012, Almirall also signed an agreement by
which Forest Laboratories sublicensed its commercialization rights for
linaclotide in Mexico to Almirall.
Notes to editors
About Constella® (linaclotide)1
Linaclotide is a Guanylate Cyclase-C receptor agonist (GCCA) with
visceral analgesic and secretory activities.
Linaclotide is a 14-amino acid synthetic peptide structurally related to
the endogenous guanylin peptide family. Both linaclotide and its active
metabolite bind to the GC-C receptor, on the luminal surface of the
intestinal epithelium. Through its action at GC-C, linaclotide has been
shown to reduce visceral pain and increase GI transit in animal models
and increase colonic transit in humans. Activation of GC-C results in an
increase in concentrations of cyclic guanosine monophosphate (cGMP),
both extracellularly and intracellularly. Extracellular cGMP decreases
pain-fiber activity, resulting in reduced visceral pain in animal
models. Intracellular cGMP causes secretion of chloride and bicarbonate
into the intestinal lumen, through activation of the cystic fibrosis
transmembrane conductance regulator (CFTR), which results in increased
intestinal fluid and accelerated transit.
Constella® is a trademark owned by Ironwood Pharmaceuticals,
Inc.
Clinical efficacy and safety1
The efficacy of linaclotide was established in two randomised,
double-blind, placebo-controlled Phase 3 clinical studies in patients
with IBS-C. In one clinical study (study 1), 802 patients were treated
with Constella® 290 micrograms or placebo once daily for 26
weeks. In the second clinical study (study 2), 800 patients were treated
for 12 weeks, and then re-randomised for an additional 4 weeks treatment
period. During the 2-weeks pre-treatment baseline period, patients had a
mean abdominal pain score of 5.6 (0-10 scale) with 2.2% of abdominal
pain-free days, a mean bloating score of 6.6 (0-10 scale), and an
average of 1.8 spontaneous bowel movements (SBM)/week.
The characteristics of the patient population included in Phase 3
clinical trials were as follows: mean age of 43.9 years [range 18 - 87
years with 5.3% ≥ 65 years of age], 90.1% female. All patients met Rome
II criteria for IBS-C and were required to report a mean abdominal pain
score of ≥ 3 on a 0-to-10-point numeric rating scale (criteria that
correspond to a moderate to severe IBS population), < 3 complete
spontaneous bowel movements and ≤ 5 SBMs per week during a 2-week
baseline period.
The co-primary endpoints in both clinical studies were 12-week IBS
degree of relief responder rate and 12 week abdominal pain/discomfort
responder rate. An IBS degree of relief responder was a patient that was
considerably or completely relieved for at least 50% of the treatment
period; an abdominal pain/discomfort responder was a patient that had an
improvement of 30% or more for at least 50% of the treatment period.
For the 12 weeks data, study 1 shows that 39% of the patients treated
with linaclotide compared with 17% of the patients treated with placebo
showed response to IBS degree of relief (p < 0.0001) and 54% of the
patients treated with linaclotide compared with 39% of the patients
treated with placebo showed response to abdominal pain/discomfort
(p < 0.0001). Study 2 shows that 37% of the patients treated with
linaclotide compared with 19% of the patients treated with placebo
showed response to IBS degree of relief (p < 0.0001) and 55% of the
patients treated with linaclotide compared with 42% of the patients
treated with placebo showed response to abdominal pain/discomfort
(p=0.0002).
For the 26 weeks data, study 1 shows that 37% and 54% of the patients
treated with linaclotide compared with 17% and 36% of the patients
treated with placebo showed response to IBS degree of relief (p < 0.0001)
and abdominal pain/discomfort (p < 0.0001) respectively.
In both studies, these improvements were seen by week 1 and sustained
over the entire treatment periods. Linaclotide has been shown not to
cause rebound effect when the treatment was stopped after 3 months
continuous treatment.
Other signs and symptoms of IBS-C including bloating, complete
spontaneous bowel movement (CSBM) frequency, straining, stool
consistency, were improved in linaclotide treated patients vs. placebo
(p < 0.0001). These effects were reached at 1 week and sustained over the
entire treatment periods.
Treatment with linaclotide also resulted in significant improvements in
validated and disease-specific Quality of Life (QoL) measure (IBS-QoL;
p < 0.0001), and EuroQoL (p = 0.001). Clinically meaningful response in
overall IBS-QoL ( > 14 points difference) was achieved in 54% of
linaclotide treated patients vs. 39% in placebo treated patients.
The most frequently reported adverse reaction associated with
linaclotide therapy was diarrhoea, mainly mild to moderate in intensity,
occurring in less than 20% of patients. Other common adverse reactions
( > 1%) were abdominal pain, abdominal distension and flatulence.
About Irritable Bowel Syndrome with Constipation (IBS-C)
IBS is defined as a functional bowel disorder in which abdominal pain or
discomfort is associated with defecation or a change in bowel function
and with features of disordered defecation.2 IBS-C is one of
four clinically different subtypes of IBS. One-third of patients with
IBS are thought to have IBS-C3 and suffer chronically from
both abdominal pain and constipation.
The Rome III Diagnostic Criteria for Functional Gastrointestinal
Disorders includes criterion for the diagnosis of IBS3 as:
-
Recurrent abdominal pain or discomfort at least three days/month, in
the last three months with symptom onset at least 6 months prior to
diagnosis, associated with two or more of the following:
-
improvement with defecation
-
onset associated with a change of frequency of stool
-
onset associated with a change in form (or appearance) of stool
The estimated prevalence of IBS at 10-15% of the European population
puts it in line with conditions such as migraine (12%) and asthma (11%)1.
IBS can have a negative impact on daily living with considerable
socio-economic and psychological consequences, and represents a major
proportion of gastrointestinal workload in both primary and secondary
care. Due to the complex, multimodal nature of the condition there is no
cure for IBS and there are minimal therapeutic options.4
About Almirall
Almirall is an international pharmaceutical company based on innovation
and committed to health. Headquartered in Barcelona, it researches,
develops, manufactures and commercialises its own R&D and licensed drugs
with the aim of improving people's health and wellbeing. Almirall
focuses its research resources on respiratory, gastrointestinal,
dermatology and pain. Almirall's products are currently present in over
70 countries in the five continents. With the opening of the Canadian
affiliate, Almirall has now direct presence in Europe, Mexico and Canada
through 13 affiliates.
For further information please visit: www.almirall.com
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (NASDAQ: IRWD) is an entrepreneurial
pharmaceutical company dedicated to the art and science of great
drugmaking. Ironwood is located in Cambridge, Mass.
To learn more, visit www.ironwoodpharma.com.
This press release contains forward looking statements. Investors
are cautioned not to place undue reliance on these forward-looking
statements, including, but not limited to, the potential for Constella
as a treatment option for the symptomatic treatment of moderate to
severe IBS-C in adult men and women, the anticipated launch timing of
Constella, and the potential for linaclotide to achieve marketing
authorization approval in countries outside of the European Union. Each
forward-looking statement is subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied in such statement. Applicable risks and uncertainties include
the risks that Constella is priced at a point lower than anticipated,
Almirall is unable to secure sufficient reimbursement for Constella in
any of the major E.U. countries, physicians do not view Constella as an
effective or safe treatment option for adult men or women who suffer
from moderate to severe IBS-C, or Almirall is unable to produce an
adequate commercial supply of Constella, as well as risks related to the
difficulty of predicting regulatory approvals, the acceptance of and
demand for new pharmaceutical products, the potential prescribing habits
of doctors, the impact of competitive products and pricing, and whether
linaclotide will ever be commercialized successfully in a given country.
Applicable risks also include those that are listed in Ironwood
Pharmaceuticals' Quarterly Report on Form 10-Q for the quarter ended
September 30, 2012, in addition to the risk factors that are listed from
time to time in Ironwood Pharmaceuticals' Annual Reports on Form 10-K,
Quarterly Reports on Form 10-Q and any subsequent SEC filings. We
undertake no obligation to update these forward-looking statements to
reflect events or circumstances occurring after this press release.
These forward-looking statements speak only as of the date of this press
release. All forward-looking statements are qualified in their entirety
by this cautionary statement.
References
1 P. S. Hungin et al - The prevalence, patterns and impact of
irritable bowel syndrome: an international survey of 40,000 subjects -
Aliment Pharmacol Ther 2003; 17: 643—650.
2 Longstreth GF, Thompson WG, Chey WD et al. - Functional
Bowel Disorders. Gastroenterology 2006; 130: 1480-1491
3American College of Gastroenterology Task Force on
Irritable Bowel Syndrome. An evidence-based position statement on the
management of irritable bowel syndrome. Am J Gastroenterol 2009;
104 Suppl 1:S1-35
4 Camilleri M, Chang L. - Challenges to the therapeutic
pipeline for irritable bowel syndrome: end points and regulatory
hurdles. Gastroenterology 2008;135:1877—1891
Almirall
Media Enquires:
Bianca Daneshfar-Nia,
+44 20 76113510
bianca.daneshfar-nia@ketchumpleon.com
or
Investor
Relations:
Jordi Molina, +34 93 2913087
jordi.molina@almirall.com
or
Ironwood
Pharmaceuticals, Inc.
Media Relations:
Lisa
Buffington, 617-374-5103
lbuffington@ironwoodpharma.com
or
Investor
Relations:
Meredith Kaya, 617-374-5082
mkaya@ironwoodpharma.com
Source: Ironwood Pharmaceuticals, Inc. and Almirall
News Provided by Acquire Media