– Commercial products expected to drive >25% compound annual growth
rate (CAGR) for Ironwood revenue between 2016 and 20201;
pipeline of innovative product candidates expected to accelerate
high-margin revenue growth into late 2020s and beyond –
– Near-term catalysts highlighted for key programs including IW-3718,
IW-1973 and linaclotide delayed release-1 –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Mar. 9, 2017--
Pharmaceuticals, Inc. (NASDAQ:IRWD), a commercial biotechnology
company, is hosting an R&D Day today, Thursday, March 9, 2017, beginning
at 9:00 a.m. Eastern Time, at its headquarters in Cambridge, Mass.
During the event, the company will present its progress delivering
innovative medicines to patients and building a top-performing
commercial biotech, with a focus on clinical and commercial strategies
for three key pipeline programs: IW-3718 for uncontrolled
gastroesophageal reflux disease (uGERD); IW-1973 for resistant
hypertension (rHTN), heart failure with preserved ejection fraction
(HFpEF) and diabetic nephropathy (DN); and linaclotide delayed release-1
(DR1) for irritable bowel syndrome with constipation (IBS-C).
This Smart News Release features an interactive multimedia capsule. View the full release here:
“Ironwood’s investments in innovation are delivering value for patients
and shareholders: we expect to have one of the fastest-growing toplines
in the biotech sector from 2016 through 2020,” said Peter Hecht, chief
executive officer of Ironwood. “Additionally, our mid- to late-stage
pipeline is advancing, with a string of recent successes and with
multiple near-term value-creating catalysts expected. We believe these
next anticipated products will accelerate high-margin growth into the
late 2020s and beyond.”
Highlights of Key Programs
IW-3718 for Uncontrolled Gastroesophageal
Reflux Disease (uGERD)
Ironwood has completed enrollment in a Phase IIb dose-ranging clinical
trial of IW-3718, and data from this trial are expected in mid-2017. The
company believes positive data would substantially reduce one of the
more significant risks in the program, and that this potential medicine
could generate greater than $2 billion in estimated U.S. annual peak
Unmet need: An estimated 10 million people in the U.S. suffer from
uGERD, and many millions more suffer globally. This distinct
population of patients is taking proton pump inhibitors (PPIs) and
continues to experience heartburn symptoms. Data from physician
surveys indicate a treatment offering a modest improvement in symptom
relief over PPIs alone would be expected to result in physician
Program rationale: IW-3718, an investigational gastric retentive
formulation of a bile acid sequestrant, is being evaluated to assess
its safety and efficacy – including its effect on heartburn severity –
when used on top of ongoing PPI therapy in patients with uGERD. Data
from a Phase IIa study demonstrated that approximately two-thirds of
patients who underwent bile reflux monitoring tested positive for bile
reflux into the esophagus, and that patients with ongoing or recent
esophagitis indicating they were actively refluxing bile or gastric
acid who received IW-3718 with their PPI demonstrated encouraging
improvements in relief of heartburn.
Next steps: The data from the Phase IIb trial expected mid-year will
include two key analyses: 1) degree of reduction in heartburn severity
for IW-3718 plus PPI versus PPI alone, and 2) define the level for a
clinically meaningful improvement based on a patient-reported outcome
measure incorporated into the study, and correlate with IW-3718
treatment effects. Given the severity of symptoms in this patient
population, the lack of prescription treatment options, industry
analogs and market research, Ironwood currently believes an
improvement in heartburn severity of at least 15% for IW-3718 plus PPI
versus PPI alone would be meaningful to patients and physicians.
IW-1973 for Resistant Hypertension (rHTN),
Heart Failure with Preserved Ejection Fraction (HFpEF) and Diabetic
In 2017, Ironwood expects to initiate Phase II clinical trials
evaluating the investigational soluble guanylate cyclase (sGC)
stimulator IW-1973 in three indications: rHTN, HFpEF and DN. The company
believes IW-1973 could generate annual peak sales greater than $5
Unmet need: rHTN, HFpEF and DN are estimated to impact 7 million, 3
million and 8 million patients in the U.S. alone, respectively, and
many millions more globally. There are a limited number of treatment
options available for these conditions, which are associated with
significant morbidity and mortality.
Program rationale: Dysregulation of the nitric oxide-soluble guanylate
cyclase-cyclical guanosine monophosphate (NO-sGC-cGMP) signaling
pathway is believed to be linked to multiple vascular and fibrotic
diseases, such as rHTN, HFpEF and DN. IW-1973 modulated the
NO-sGC-cGMP pathway and improved vascular function, vascular
inflammation, fibrosis and metabolism in nonclinical studies.
Next steps: Ironwood expects to initiate Phase II clinical trials with
IW-1973 in all three indications during the second half of 2017.
Linaclotide Delayed Release-1 for Irritable
Bowel Syndrome with Constipation (IBS-C)
LINZESS® (linaclotide) is on track to exceed $1 billion in
annual U.S. net sales by 2020; LINZESS and linaclotide DR1, if approved,
would be expected to co-exist in the market for more than a decade and
achieve greater than $2 billion in U.S. annual peak sales.
Unmet need: Market research has shown that abdominal pain is the most
bothersome symptom for IBS-C patients and is what motivates them to
seek treatment. Physicians and patients rate LINZESS highly for its
effective relief of abdominal pain.
Program rationale: Linaclotide DR1, an investigational medicine, is
being studied to determine if it can provide 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, and
if it can improve abdominal pain relief in patients with IBS-C. Phase
IIb data demonstrated that 300 mcg linaclotide DR1 resulted in
numerically greater abdominal pain improvement compared to placebo and
to the 290 mcg immediate release (IR) formulation of linaclotide.
Next steps: Ironwood and Allergan intend to begin a Phase III program
for linaclotide DR1 in adults with IBS-C in the second half of 2017,
pending discussions with FDA.
The R&D Day event will be accessible through the Investors section of
the company’s website at www.ironwoodpharma.com.
To access the webcast, please log on to the Ironwood website at least 15
minutes prior to the start of the call to ensure adequate time for any
software downloads that may be required. 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
75432701. The webcast will be available for replay via telephone
starting March 9, 2017 at approximately 2:00 p.m. Eastern Time, running
through 3:00 p.m. Eastern Time on March 16, 2017. To listen to the
replay, dial (855) 859-2056 (U.S. and Canada) or (404) 537-3406
(international) using conference ID number 75432701. The archived
webcast will be available on Ironwood’s website for 14 days beginning
approximately one hour after the webcast has completed.
About LINZESS (linaclotide)
LINZESS is the #1 prescribed brand for the treatment of adult patients
with irritable bowel syndrome with constipation (IBS-C) and chronic
idiopathic constipation (CIC), based on QuintilesIMS data. Since its FDA
approval in August of 2012 and subsequent launch in December 2012,
nearly 1.5 million unique patients have filled nearly 7 million
prescriptions for LINZESS, according to QuintilesIMS.
LINZESS is a once-daily capsule that helps relieve the abdominal pain
and constipation associated with IBS-C, as well as the constipation,
infrequent stools, hard stools, straining and incomplete evacuation
associated with CIC. The recommended dose is 290 mcg for IBS-C patients
and 145 mcg for CIC patients, with a 72 mcg dose approved for use in CIC
depending on individual patient presentation or tolerability. LINZESS
should be taken at least 30 minutes before the first meal of the day.
LINZESS is contraindicated in pediatric patients less than 6 years of
age. The safety and effectiveness of LINZESS in pediatric patients less
than 18 years of age have not been established. In neonatal mice,
linaclotide increased fluid secretion as a consequence of GC-C agonism
resulting in mortality within the first 24 hours due to dehydration. Due
to increased intestinal expression of GC-C, patients less than 6 years
of age may be more likely than patients 6 years of age and older to
develop severe diarrhea and its potentially serious consequences. In
adults with IBS-C or CIC treated with LINZESS, the most commonly
reported adverse event was diarrhea.
LINZESS is not a laxative; it is the first medicine approved by the FDA
in a class called guanylate cyclase-C (GC-C) agonists. LINZESS contains
a peptide called linaclotide that is structurally related to the
naturally occurring peptides guanylin and uroguanylin, which activate
the GC-C receptor in the intestine. Activation of GC-C is thought to
result 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.
In the United States, Ironwood and Allergan plc co-develop and
co-commercialize LINZESS for the treatment of adults with IBS-C or CIC.
In Europe, Allergan markets linaclotide under the brand name CONSTELLA®
for the treatment of adults with moderate to severe IBS-C. In Japan,
Ironwood's partner Astellas received approval of linaclotide 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 and with Allergan for development and
commercialization of linaclotide in all other territories worldwide.
LINZESS Important Safety Information
INDICATIONS AND USAGE
LINZESS (linaclotide) is indicated in adults for the treatment of both
irritable bowel syndrome with constipation (IBS-C) and chronic
idiopathic constipation (CIC).
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS
LINZESS is contraindicated in patients less than 6 years of
age. In nonclinical studies in neonatal mice, administration of a
single, clinically relevant adult oral dose of linaclotide caused
deaths due to dehydration. Use of LINZESS should be avoided in
patients 6 years to less than 18 years of age. The safety and
effectiveness of LINZESS have not been established in patients
less than 18 years of age.
LINZESS is contraindicated in patients less than 6 years of age due to
the risk of serious dehydration.
LINZESS is contraindicated in patients with known or suspected
mechanical gastrointestinal obstruction.
Warnings and Precautions
LINZESS is contraindicated in patients less than 6 years of age. The
safety and effectiveness of LINZESS in patients less than 18 years of
age have not been established. In neonatal mice, linaclotide increased
fluid secretion as a consequence of GC-C agonism resulting in
mortality within the first 24 hours due to dehydration. Due to
increased intestinal expression of GC-C, patients less than 6 years of
age may be more likely than patients 6 years of age and older to
develop severe diarrhea and its potentially serious consequences.
Use of LINZESS should be avoided in pediatric patients 6 years to less
than 18 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 years to less than 18 years of age.
Diarrhea was the most common adverse reaction in LINZESS-treated
patients in the pooled IBS-C and CIC double-blind placebo-controlled
trials. The incidence of diarrhea was similar in the IBS-C and CIC
populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg
LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC
patients. If severe diarrhea occurs, dosing should be suspended and
the patient rehydrated.
Common Adverse Reactions (incidence ≥2% and greater than placebo)
In IBS-C clinical trials: 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 trials of a 145 mcg dose: 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%). In a CIC trial of a 72 mcg dose: diarrhea (19%
vs 7% placebo) and abdominal distension (2% vs <1%).
Please see full Prescribing Information including Boxed Warning: http://www.allergan.com/assets/pdf/linzess_pi
About Uncontrolled Gastroesophageal Reflux Disease
An estimated 10 million people in the U.S. suffer from uncontrolled
gastroesophageal reflux disease (uGERD); this distinct population of
patients continues to experience symptoms such as heartburn and
regurgitation despite receiving the current standard of care treatment
with a proton pump inhibitor (PPI). While PPIs suppress production of
stomach acid, research suggests reflux of bile from the intestine into
the stomach and esophagus may play a role in the ongoing symptoms of
uGERD. There are no FDA-approved prescription treatment options for
these patients. If left untreated, uGERD can lead to serious
complications including Barrett’s esophagus and, in rare instances,
IW-3718 is a novel, investigational gastric retentive formulation of a
bile acid sequestrant, developed by Ironwood using the proprietary
Acuform® drug delivery technology licensed from Depomed, Inc.
IW-3718 is designed to remain in the stomach and duodenum (upper small
intestine) over an extended period of time and to work in combination
with a PPI to reduce the detrimental effects of bile and acid on the
About Ironwood’s sGC Program
Soluble guanylate cyclase (sGC), a central component of the NO-sGC-cGMP
pathway, plays an important role in regulating diverse physiological
processes such as blood flow, inflammation, fibrosis, and metabolism.
Dysregulation of sGC may play a role in multiple vascular and fibrotic
diseases with high unmet need such as diabetic nephropathy, resistant
hypertension, heart failure, achalasia, sickle cell disease and vascular
dementia. Ironwood established its expertise in this signaling pathway
through the discovery and development of linaclotide, a guanylate
cyclase C (GC-C) agonist. Stimulation of sGC is a clinically validated
approach, and Ironwood leveraged its GC-C expertise to discover and
develop multiple sGC stimulators. IW-1973 is currently being studied in
diabetes patients with hypertension and IW-1701 is being studied in
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 commercializing two innovative primary care
products: linaclotide, the U.S. branded prescription market leader for
adults with irritable bowel syndrome with constipation (IBS-C) or
chronic idiopathic constipation (CIC), and lesinurad, which is approved
to be taken with a xanthine oxidase inhibitor (XOI) for the treatment of
hyperuricemia associated with uncontrolled gout. We are also advancing a
pipeline of internally and externally generated innovative product
candidates in areas of significant unmet need, including uncontrolled
gastroesophageal reflux disease and vascular and fibrotic diseases.
Ironwood was founded in 1998 and is headquartered in Cambridge, Mass.
For more information, please visit www.ironwoodpharma.com
information that may be important to investors will be routinely posted
in both these locations.
LINZESS® and CONSTELLA® are trademarks of Ironwood
Pharmaceuticals, Inc. Any other trademarks referred to in this press
release are the property of their respective owners. All rights reserved.
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about the development, launch,
introduction and commercial potential of linaclotide, lesinurad, our
product candidates and the other products that we promote and the
drivers, timing, impact and results thereof (including near-term
value-creating catalysts); reduction of a significant risk from IW-3718,
if Phase IIb data is positive; market size, prevalence, growth and
opportunity, including peak sales and the potential demand for
linaclotide, lesinurad and our product candidates, as well as their
potential impact on applicable markets; the potential indications for,
and benefits of, linaclotide, lesinurad and our product candidates; the
anticipated timing of preclinical, clinical and regulatory developments
and the design, timing and results of clinical and preclinical studies;
the potential for, and timing of, regulatory submissions and approvals
for linaclotide, lesinurad and our product candidates, and the level of
risk associated with the path to approval; expected periods of patent
exclusivity; the strength of the intellectual property protection for
linaclotide, lesinurad and our product candidates and our intentions and
efforts to protect such intellectual property; our potential for
sustainable, high-margin growth and shareholder returns; consensus
expectations related to revenue growth for certain commercial biotech
companies; expectations concerning if and when we will become cash flow
positive; and our financial performance and results, and guidance and
expectations related thereto (including the drivers and timing thereof),
including expectations related to Ironwood revenue CAGR, cash flow
accretion, margin expansion and revenue growth, LINZESS U.S. net sales
and growth, commercial margin and commercial costs, LINZESS
profitability and Ironwood revenues. 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 the
effectiveness of development and commercialization efforts by us and our
partners; preclinical and clinical development, manufacturing and
formulation development; our reliance on AstraZeneca to provide critical
support services related to lesinurad; the risk that findings from our
completed nonclinical and clinical studies may not be replicated in
later studies; efficacy, safety and tolerability of linaclotide,
lesinurad and our product candidates; decisions by regulatory
authorities; the risk that we are unable to successfully integrate
lesinurad into our existing business, commercialize lesinurad or realize
the anticipated benefits of the lesinurad transaction; 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; the outcomes in legal proceedings to protect or enforce the
patents relating to our products and product candidates, including ANDA
litigation; developments in the intellectual property landscape;
challenges from and rights of competitors or potential competitors; the
risk that our planned investments do not have the anticipated effect on
our company revenues, linaclotide, lesinurad or our product candidates;
the risk that we are unable to manage our operating expenses or cash use
for operations, or are unable to commercialize our products, within the
guided ranges or otherwise as expected; and the risks listed under the
heading "Risk Factors" and elsewhere in Ironwood's Annual Report on Form
10-K for the year ended December 31, 2016, and in our subsequent SEC
filings. These forward-looking statements (except as otherwise noted)
speak only as of the date of this press release, and Ironwood undertakes
no obligation to update these forward-looking statements.
1 The >25% Ironwood revenue CAGR calculation excludes any
current or future revenue recognized in the period related to milestone
payments to Ironwood, including approximately $39 million recognized in
View source version on businesswire.com: http://www.businesswire.com/news/home/20170309005647/en/
Source: Ironwood Pharmaceuticals, Inc.
Ironwood Pharmaceuticals, Inc.
Director, Corporate Communications
Meredith Kaya, 617-374-5082