Abdominal pain improved 56% with CR1 300 mcg relative to placebo
in this trial
Companies separately announced Phase IIb data with linaclotide
colonic release-2 (CR2) supporting investigation in additional GI
indications associated with abdominal pain
Ironwood to host conference call today at 8:30 a.m. Eastern Time
CAMBRIDGE, Mass. & DUBLIN--(BUSINESS WIRE)--
Ironwood
Pharmaceuticals, Inc. (NASDAQ:IRWD) and Allergan
plc (NYSE:AGN) announced today positive topline data from a Phase
IIb clinical trial evaluating the investigational linaclotide colonic
release-1 (CR1) formulation in adult patients with irritable bowel
syndrome with constipation (IBS-C). Topline data in this trial
demonstrated numerically greater abdominal pain improvement with CR1 300
mcg compared to placebo and to the 290 mcg immediate release (IR)
formulation of linaclotide. The companies intend to engage with the U.S.
Food and Drug Administration (FDA) to discuss Phase III development
plans, with trials in adults with IBS-C expected to begin in the second
half of 2017.
Linaclotide IR (LINZESS®) is currently FDA-approved and
available for the treatment of adults with IBS-C or chronic idiopathic
constipation (CIC). Linaclotide is thought to work in two ways, based on
non-clinical studies: by decreasing the activity of pain-sensing nerves
and by increasing fluid secretion into the intestine. Linaclotide CR1 is
designed to provide targeted delivery of linaclotide to the distal small
intestine and colon, where the majority of the abdominal pain
associated with IBS-C is believed to originate. This clinical trial was
designed to evaluate whether CR1 could further decrease the activity of
key pain-sensing nerves in the distal small intestine and colon
while maintaining an effect on fluid secretion. Ironwood and Allergan
also announced topline results from the same Phase IIb trial with a
second formulation, linaclotide colonic release-2 (CR2), in a separate
press release issued today.
"Abdominal pain is usually the most difficult symptom to treat in
patients with IBS-C. When that pain is not treated sufficiently, then
that drives the patient back into my office again and again," said
Philip Schoenfeld, M.D., chief, gastroenterology section, John D.
Dingell VA Medical Center and adjunct professor of medicine at the
University of Michigan School of Medicine. "I'm encouraged by these
initial data. This new formulation of linaclotide may produce additional
relief of abdominal pain in patients with IBS-C."
The double-blind, placebo-controlled, dose-ranging Phase IIb trial
randomized 532 adult patients with IBS-C into one of eight possible
treatment arms. The trial was exploratory in nature and comparisons to
placebo were evaluated using nominal p-values. In the trial, CR1 300 mcg
demonstrated improvement on the three prespecified key efficacy
endpoints as follows:
-
6/12 APC+1 Responder: the percentage of patients to report at
least a 30% reduction from baseline in abdominal pain and an increase
of at least one complete spontaneous bowel movement (CSBM) from
baseline, both in the same week for at least 6 out of 12 weeks, was
38.8% for CR1 300 mcg compared to 21.2% for placebo and 31.8% for IR
290 mcg.
-
Change from Baseline in Abdominal Pain: the average weekly
change in abdominal pain from baseline to week 12 was -2.14 for CR1
300 mcg compared to -1.37 for placebo and -1.94 for IR 290 mcg, as
measured on an 11-point scale. This translates to a 56.2% improvement
in abdominal pain with CR1 300 mcg relative to placebo.
-
Change from Baseline in CSBM Frequency: the average weekly
change in CSBM frequency from baseline to week 12 was 1.78 for CR1 300
mcg compared to 1.11 for placebo and 2.11 for IR 290 mcg. This
translates to a 59.3% improvement in CSBM frequency with CR1 300 mcg
relative to placebo.
In this trial, CR1 300 mcg showed a numerically greater reduction in
abdominal pain than IR 290 mcg each week beginning at week 5 and
continuing for the remainder of the 12 week study, with a mean percent
reduction from baseline at week 12 of 49.5% for CR1 300 mcg compared to
26.2% for placebo and 40.6% for IR 290 mcg. Additionally, patients
treated with linaclotide CR1 300 mcg reported improvement in other
abdominal and bowel symptoms commonly experienced by IBS-C patients,
including abdominal discomfort and bloating.
The most common adverse event was diarrhea, which was reported in 10.4%
of patients on CR1 300 mcg compared to 1.5% of patients on placebo and
13.6% of patients on IR 290 mcg. All diarrhea adverse events reported
were mild or moderate in severity, with discontinuation resulting from
diarrhea occurring in 3.0% of CR1 300 mcg patients compared to no
placebo patients and 6.1% of IR 290 mcg patients.
Additional data from the Phase IIb trial are expected to be shared at
upcoming scientific meetings and via peer-reviewed publications.
"Relief of abdominal pain is a key benefit motivating physicians to
choose LINZESS for patients suffering from IBS-C, and it is the primary
driver of patient satisfaction," said Tom McCourt, chief commercial
officer of Ironwood. "We believe the potentially enhanced clinical
profile of linaclotide CR1 could support further growth of the LINZESS
franchise from $1 billion in U.S. net sales by 2020 to potentially
greater than $2 billion in peak U.S. net sales."
"LINZESS is the market-leading U.S. branded prescription medicine for
adults with IBS-C or CIC and has been utilized by more than 1 million
patients to date," said Bill Meury, chief commercial officer of
Allergan. "The CR1 formulation could provide an innovative brand to
treat millions of additional suffering patients, extending the success
of LINZESS and demonstrating our continued commitment to improving GI
care."
Ironwood and Allergan are pursuing patent protection for CR1 and CR2
that, if issued, is expected to provide patent coverage into the
mid-2030s.
Ironwood Conference Call Today at 8:30 a.m. ET:
Ironwood will host a conference call and webcast at 8:30 a.m. Eastern
Time on Thursday, December 22, to discuss the results of the linaclotide
colonic release Phase IIb clinical trial. Individuals interested in
participating in the call should dial (877) 643-7155 (U.S. and
Canada) or (914) 495-8552 (international) using conference ID number
43363931. To access the webcast, please visit the Investors section of
Ironwood's website at www.ironwoodpharma.com
at least 15 minutes prior to the start of the call to ensure adequate
time for any software downloads that may be required. The call will be
available for replay via telephone starting at approximately 11:30 a.m.
Eastern Time, on December 22, running through 11:59 p.m. Eastern Time on
December 29, 2016. To listen to the replay, dial (855) 859-2056 (U.S.
and Canada) or (404) 537-3406 (international) using conference ID number
43363931. The archived webcast will be available on Ironwood's website
for 14 days beginning approximately one hour after the call has
completed.
Study Design
Patients in the double-blind, placebo-controlled, dose-ranging Phase IIb
clinical trial were randomized to one of eight groups: one group
received placebo, one group received linaclotide 290 mcg (approved
formulation), three groups received various doses of linaclotide CR1 (30
mcg, 100 mcg or 300 mcg), and three groups received various doses of
linaclotide CR2 (30 mcg, 100 mcg or 300 mcg). The 290 mcg approved
formulation was included as a reference group for this study. The trial
was designed to evaluate the safety and efficacy of each linaclotide
colonic release dose and formulation relative to placebo; the
statistical power was based on a linear dose response. Additional
objectives included assessing how the two colonic release formulations
compared to each other and to the approved 290 mcg formulation of
linaclotide. All doses were administered orally, once daily for 12 weeks.
About Irritable Bowel Syndrome with Constipation
Irritable bowel syndrome with constipation (IBS-C) is a functional
gastrointestinal disorder in which individuals experience hallmark
symptoms of abdominal pain and infrequent bowel movements (less than
three times per week). While estimates vary, as many as 13 million
adults in the U.S. may suffer from IBS-C. Results derived from responses
to a web based survey commissioned by Forest Pharmaceuticals and
Ironwood Pharmaceuticals suggest that only about half of adult IBS-C
sufferers are medically diagnosed. There are few available prescription
treatment options for this condition.
About Linaclotide
Linaclotide is a guanylate cyclase‐C (GC‐C) agonist that is thought to
work in two ways based on nonclinical studies. Linaclotide binds to the
GC-C receptor locally, within the intestinal epithelium. Activation of
GC-C results in increased intestinal fluid secretion and accelerated
transit and a decrease in the activity of pain-sensing nerves in the
intestine. The clinical relevance of the effect on pain fibers, which is
based on nonclinical studies, has not been established. Linaclotide is
marketed by Ironwood and Allergan in the United States as LINZESS®
and is indicated for the treatment of adults with irritable bowel
syndrome with constipation (IBS-C) or chronic idiopathic constipation
(CIC). Linaclotide is marketed by Allergan for the treatment of adults
with moderate to severe IBS-C in Europe under the brand name CONSTELLA®.
Ironwood's partner Astellas received approval of linaclotide in Japan
under the brand name LINZESS® for the treatment of adults with IBS-C.
Ironwood also has partnered with AstraZeneca for development and
commercialization of linaclotide in China.
LINZESS Important Safety Information
____________________________________________________________________________
WARNING: PEDIATRIC RISK
LINZESS is contraindicated in pediatric patients under 6 years of
age. In nonclinical studies, administration of a single, clinically
relevant adult oral dose of linaclotide caused deaths due to dehydration
in young juvenile mice. Use of LINZESS should be avoided in pediatric
patients 6 through 17 years of age. The safety and efficacy of LINZESS
has not been established in pediatric patients under 18 years of age.
____________________________________________________________________________
Contraindications
-
LINZESS is contraindicated in pediatric patients under 6 years of age.
-
LINZESS is contraindicated in patients with known or suspected
mechanical gastrointestinal obstruction.
Warnings and Precautions
Pediatric Risk
-
LINZESS is contraindicated in children under 6 years of age. The
safety and effectiveness of LINZESS in pediatric patients under 18
years of age have not been established. In neonatal mice, increased
fluid secretion as a consequence of GC-C agonism resulted in mortality
within the first 24 hours due to dehydration. Due to increased
intestinal expression of GC-C, children under 6 years of age may be
more likely than older children and adults to develop significant
diarrhea and its potentially serious consequences.
-
Use of LINZESS should be avoided in pediatric patients 6 through 17
years of age. Although there were no deaths in older juvenile mice,
given the deaths in young juvenile mice and the lack of clinical
safety and efficacy data in pediatric patients, use of LINZESS should
be avoided in pediatric patients 6 through 17 years of age.
Diarrhea
-
Diarrhea was the most common adverse reaction of LINZESS-treated
patients in the pooled IBS-C and CIC double-blind placebo-controlled
trials. Severe diarrhea was reported in 2% of LINZESS-treated
patients. The incidence of diarrhea was similar in the IBS-C and CIC
populations.
-
Patients should be instructed to stop LINZESS if severe diarrhea
occurs and to contact their healthcare provider. The healthcare
provider should consider dose suspension and rehydration.
Adverse Reactions
-
In IBS-C clinical trials, the most common adverse reactions in
LINZESS-treated patients (incidence ≥2% and greater than placebo) were
diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence
(4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and
abdominal distension (2% vs 1%).
-
In CIC clinical trials, the most common adverse reactions in
LINZESS-treated patients (incidence ≥2% and greater than placebo) were
diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence
(6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis
(3% vs 2%) and abdominal distension (3% vs 2%).
Please see full Prescribing Information including Boxed Warning: http://www.allergan.com/assets/pdf/linzess_pi
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (NASDAQ: IRWD) is a commercial biotechnology
company focused on creating medicines that make a difference for
patients, building value for our fellow shareholders, and empowering our
passionate team. We are advancing a pipeline of innovative medicines in
areas of significant unmet need, including irritable bowel syndrome with
constipation (IBS-C)/chronic idiopathic constipation (CIC), uncontrolled
gout, refractory gastroesophageal reflux disease, and vascular and
fibrotic diseases. We discovered, developed and are commercializing
linaclotide, the U.S. branded prescription market leader in the
IBS-C/CIC category, and we are applying our proven R&D and commercial
capabilities to advance multiple internally-developed and
externally-accessed product opportunities. Ironwood was founded in 1998
and is headquartered in Cambridge, Mass. For more information, please
visit www.ironwoodpharma.com or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold,
global pharmaceutical company and a leader in a new industry model -
Growth Pharma. Allergan is focused on developing, manufacturing and
commercializing branded pharmaceuticals, devices and biologic products
for patients around the world.
Allergan markets a portfolio of leading brands and best-in-class
products for the central nervous system, eye care, medical aesthetics
and dermatology, gastroenterology, women's health, urology and
anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, the Company's R&D model,
which defines our approach to identifying and developing game-changing
ideas and innovation for better patient care. This approach has led
to Allergan building one of the broadest development pipelines in the
pharmaceutical industry with 65+ mid-to-late stage pipeline programs in
development.
Our Company's success is powered by our more than 16,000 global
colleagues' commitment to being Bold for Life. Together, we build
bridges, power ideas, act fast and drive results for our customers and
patients around the world by always doing what is right.
With commercial operations in approximately 100 countries, Allergan is
committed to working with physicians, healthcare providers and patients
to deliver innovative and meaningful treatments that help people around
the world live longer, healthier lives.
For more information, visit Allergan's website at www.Allergan.com.
Forward-Looking Statement
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about the topline assessment of the
data from the Phase IIb clinical trial of CR1; the development and
regulatory plans for CR1, and the timing thereof, including further
investigation and advancement of CR1, engaging with the FDA and
advancing CR1 into Phase III; the design of the Phase IIb trial and its
impact on the results thereof; the timing of additional Phase IIb data;
the potential indications for, and benefits of, CR1; the design and
possible benefits of CR1 and its potential as a treatment for patients;
prevalence and unmet need; market size, growth and opportunity and
potential demand for CR1 in the U.S., including net sales and peak
sales; and the strength of the intellectual property protection for
linaclotide. 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 those related to preclinical and clinical
development, manufacturing and formulation development; the risk that
future clinical studies need to be discontinued for any reason,
including safety, tolerability, enrollment, manufacturing or economic
reasons; the risk that findings from our completed nonclinical and
clinical studies may not be replicated in later studies; efficacy,
safety and tolerability of linaclotide; the risk that the therapeutic
opportunities for the CR formulations are not as we expect; decisions by
regulatory authorities; those risks related to competition and future
business decisions made by us and our competitors or potential
competitors; the risk that we may never get sufficient patent protection
for linaclotide and our product candidates or that we are not able to
successfully protect such patents; developments in the intellectual
property landscape; and the risks listed under the heading "Risk
Factors" and elsewhere in Ironwood's Quarterly Report on Form 10-Q for
the quarter ended September 30, 2016, Allergan's Annual Report on Form
10-K for the year ended December 31, 2015 and in the subsequent SEC
filings of each company. These forward-looking statements (except as
otherwise noted) speak only as of the date of this press release, and
Ironwood and Allergan undertake no obligation to update these
forward-looking statements.
LINZESS and CONSTELLA are trademarks owned by Ironwood Pharmaceuticals,
Inc. Any other trademarks referred to in this press release are the
property of their respective owners. All rights reserved.
View source version on businesswire.com: http://www.businesswire.com/news/home/20161222005171/en/
Allergan
Mark Marmur, 862-261-7558
Global Corporate
Media Relations
mark.marmur@allergan.com
or
Fran
DeSena, 201-427-8762
US Product Relations
fran.desena@allergan.com
or
Lisa
DeFrancesco, 862-261-7152
Investor Relations
lisa.defrancesco@allergan.com
or
Ironwood
Pharmaceuticals, Inc.
Trista Morrison, 617-374-5095
Director,
Corporate Communications
tmorrison@ironwoodpharma.com
or
Meredith
Kaya, 617-374-5082
Director, Investor Relations
mkaya@ironwoodpharma.com
Source: Ironwood Pharmaceuticals, Inc. and Allergan
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