– New safety and tolerability data show high
treatment compliance with apraglutide, low incidence of injection
site reactions and adverse events associated with GI tolerability
–
– Findings reinforce the clinical profile of
once-weekly apraglutide; Ironwood expects to complete U.S.
regulatory submission in Q1 2025 –
– One apraglutide poster recognized as
presidential poster recipient –
– New linaclotide data shed light on treatment
outcomes across patient demographics –
Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a
GI-focused healthcare company, will present new findings at the
American College of Gastroenterology (ACG) 2024 Annual Scientific
Meeting and Postgraduate Course from subgroup analyses of the
primary endpoint of the pivotal Phase III clinical trial, STARS,
evaluating the treatment effect of apraglutide by baseline
demographics and disease-specific characteristics in adults with
short bowel syndrome with intestinal failure (SBS-IF). The data,
which will be unveiled during an oral presentation tomorrow,
October 29, from 8:30 am – 8:40 am ET, indicate that apraglutide
showed a consistent treatment effect across subgroups: gender, age,
body weight, region, race, ethnicity and SBS characteristics –
including length of remnant bowel. These findings build on
previously announced positive data from the phase III pivotal
trial.
SBS-IF, a rare chronic debilitating malabsorptive condition in
which patients are dependent on parenteral support (PS), affects an
estimated 18,000 adult patients in the U.S., Europe and Japan.
Apraglutide is the first and only investigational once-weekly GLP-2
analog that has successfully demonstrated positive results in a
Phase III placebo-controlled study. Ironwood is working to submit a
New Drug Application (NDA) to the U.S. Food and Drug Administration
(FDA) and marketing applications to other regulatory agencies for
apraglutide for the treatment of adult patients with SBS who are
dependent on PS.
STARS represents the largest Phase III trial in SBS-IF conducted
to date, and the only study that pre-specified patient
stratification based on remnant bowel anatomy. Ironwood previously
reported that the STARS clinical trial met its primary endpoint of
relative change from baseline in actual weekly PS volume at week 24
vs. placebo (-25.5% vs. -12.5%; p=0.001). The new subgroup analyses
examined the primary endpoint by demographics for the overall
population, which included patients with stoma and colon-in-
continuity: gender, age (<65 and ≥65 years old), body weight
(<50 and ≥50 kgs), region (EU, USA or rest of world), race
(Asian, Caucasian or other), ethnicity (Hispanic/Latino or not) and
SBS characteristics (PS volume, length of remnant bowel and time
from SBS diagnosis at baseline). Analyses showed consistent
treatment effect for apraglutide vs. placebo across subgroups of
varying baseline demographics and SBS characteristics in the
overall population. Significance in favor of apraglutide was shown
in body weight, PS volume at baseline, and length of remnant small
bowel, in addition to other subgroups.
“SBS-IF is a rare condition, but it is extremely variable in
terms of patient demographics and the way in which they present,”
said Kishore R Iyer, MBBS, FRCS (Eng), FACS, Director of Adult and
Pediatric Intestine Rehabilitation & Transplantation at The
Mount Sinai Hospital in New York, Coordinating Principal
Investigator of the trial, paid scientific advisor to Ironwood and
chair of the scientific steering committee for the STARS clinical
trial. “The analyses from STARS are critically important in helping
us confirm consistency of treatment effect across different
subgroups in the largest SBS-IF study ever conducted. The
consistency across different baseline volumes and lengths of
remnant bowel is especially noteworthy, given that this disease
characteristic has a significant impact on treatment and
prognosis.”
Topline results from STARS were previously announced in February
2024, and the topline data was also presented at Digestive Disease
Week® (DDW) in May.
In addition to the STARS Phase III oral presentation, Ironwood
and its collaborators presented new safety findings from the STARS
study, with this abstract receiving a Presidential Poster
Award.
“As we work to make apraglutide available as potentially the
first once-weekly treatment option for patients with SBS who are
dependent on PS, we are focused on continuing to educate the SBS
community on the potential of this compound across profiles of
adult patients given the known patient heterogeneity,” said Michael
Shetzline, M.D., Ph.D., chief medical officer, senior vice
president and head of research and drug development at Ironwood
Pharmaceuticals. “Patient demographic analyses play a key role in
understanding the impact of any medication, and our focus on these
analyses extends to all our data at ACG this year.”
In addition to the apraglutide data, Ironwood is also featuring
linaclotide data at ACG.
More details on these data are provided below.
Safety Data from STARS
“Safety and Tolerability of Once-Weekly Glucagon-like Peptide-2
Analog Apraglutide in Patients with Short Bowel Syndrome and
Intestinal Failure (SBS-IF): Results from a Global, Phase 3,
Randomized, Double-Blind Trial” (poster number 1521, Presidential
Poster Award) was presented by Mena Boules, M.D., Ironwood
Pharmaceuticals. This analysis showed that apraglutide had a safety
profile consistent with previous apraglutide studies, with no new
safety concerns. Incidence of AEs, serious AEs and AEs of Grade ≥ 3
was similar between treatment arms. Dose interruptions due to AEs
were also similar between apraglutide and placebo (10.9% vs 11.3%).
The incidence of AEs associated with gastrointestinal (GI)
tolerability was low and similar between treatment arms. Most
frequently reported AE was nausea (apraglutide 13.6% vs placebo
11.3%). Incidence of subjects with GI polyps was also low
(apraglutide n=4 [3.6%] vs placebo n=2 [3.8%]); all polyps could be
removed during colonoscopy, with no apraglutide discontinuations
due to GI tolerability symptoms or GI polyps. GI stoma complication
was reported in 7.3% of apraglutide vs 3.8% of placebo patients.
There were no cases of complete GI obstruction or malignancies. The
incidence of injection site reactions was similar between
apraglutide and placebo. There was one death in the apraglutide arm
(sudden cardiac death, unrelated). More than 98% of patients had ≥
80% treatment compliance in both treatment arms. Most patients
entered the long-term, open-label STARS Extend trial at the end of
the study (apraglutide 92% vs placebo 89%).
Linaclotide Treatment Outcomes by Patient Demographic
- “Efficacy, Safety and Time to Response of Linaclotide in Adult
Patients With Chronic Idiopathic Constipation: A Post Hoc Subgroup
Analysis by Age” (poster number P0615) was presented by Lin Chang,
M.D., Vatche and Tamar Manoukian Division of Digestive Diseases,
David Geffen School of Medicine, UCLA, Los Angeles. The results
showed that linaclotide-treated patients with CIC tended to show
greater and faster improvement in bowel and abdominal symptoms
compared with placebo and had similar safety profiles across age
groups (< 65 and ≥ 65 yrs) for both linaclotide doses (72 mcg or
145 mcg). The authors noted that the small sample size for patients
aged ≥ 65 years should be considered when interpreting these
data.
Two studies will be presented by Baha Moshiree, M.D., Division
of Gastroenterology, Advocate Health Wake Forest Medical
University, Charlotte.
- “Efficacy and Safety of Linaclotide in Patients With Chronic
Idiopathic Constipation: A Post Hoc Analysis of Phase 3 Clinical
Study Data Assessing Primary and Additional Endpoints by Race and
Ethnicity, and by Age” (poster number P2334). The study showed that
linaclotide improved complete spontaneous bowel movement (CSBM)
responder rates and CIC symptoms, and had a similar safety profile,
across most races/ethnicities and ages in CIC patients. The authors
note that small sample sizes for Asian and other patient groups
(and some age subgroups) limit data interpretation and highlight
the need to recruit more diverse populations in clinical
studies.
- “Impact of Weight on the Efficacy, Time to Response and Safety
of Linaclotide in Adults With Chronic Idiopathic Constipation or
Irritable Bowel Syndrome With Constipation: Post Hoc Descriptive
Analysis by Body Mass Index” (poster number P4073). The study
showed that linaclotide improved bowel symptoms in patients with
CIC and IBS-C and was similarly efficacious in those with normal
weight, overweight or obesity. Treatment-emergent adverse events
(TEAEs) were consistent with the known safety profile of
linaclotide.
About STARS
The STARS (STudy of ApRaglutide in SBS) pivotal Phase III trial
represents the largest Phase III trial in SBS-IF to date.
This global, multicenter, double-blind, randomized,
placebo-controlled trial evaluated the efficacy and safety of
weekly subcutaneous injections of apraglutide in adult patients
with SBS-IF. STARS randomized 164 patients 2:1 and 163 were dosed
to receive either once-weekly apraglutide or placebo. Patients were
stratified approximately 50/50 by remnant bowel anatomy (stoma vs.
colon-in continuity) and evaluated over 24 weeks (stoma and
colon-in-continuity subpopulations) and 48 weeks
(colon-in-continuity subpopulation only). The primary endpoint was
relative change from baseline in actual weekly PS volume at week
24. Key secondary endpoints included patients who achieved a
reduction from baseline of at least 1 day/week off PS at week 24
(overall population); relative change from baseline in actual
weekly PS volume at week 24 (stoma subpopulation); patients who
achieved a reduction from baseline of at least 1 day/week off PS at
week 48 (colon-in-continuity subpopulation); and patients reaching
enteral autonomy at week 48 (colon-in-continuity
subpopulation).
The study was conducted in 18 countries with enrollment from 68
study sites.
About Short Bowel Syndrome
SBS is a serious and chronic condition where there is diminished
absorptive capacity for fluids and/or nutrients, sometimes
requiring dependence on parenteral support to maintain health.
Short bowel syndrome typically occurs because of extensive
intestinal resection, and patients with SBS who are dependent on
parenteral support, also referred to as SBS with intestinal failure
(SBS-IF), often experience significant quality of life impact and
are at risk of severe complications such as infection. An estimated
18,000 adult patients suffer from SBS-IF in the U.S., Europe and
Japan, and have chronic dependence on PS, which significantly
impacts quality of life and carries the risk of severe
complications such as infection. Many of these patients often
require chronic PS infusions for 10+ hours per day. And up to 7
days a week. SBS-IF is associated with frequent complications,
significant morbidity and mortality, high economic burden, and an
impaired quality of life.
About Apraglutide
Apraglutide is an investigational, next-generation, long-acting
synthetic GLP-2 analog being developed for a range of rare
gastrointestinal diseases where GLP-2 can play a central role in
addressing disease pathophysiology, including short bowel syndrome
with intestinal failure (SBS-IF) and Acute Graft-Versus-Host
Disease (aGVHD).
About LINZESS (Linaclotide)
LINZESS® is the #1 prescribed brand in the U.S. for the
treatment of adult patients with irritable bowel syndrome with
constipation (“IBS-C”) or chronic idiopathic constipation (“CIC”),
based on IQVIA data. LINZESS is a once-daily capsule that helps
relieve the abdominal pain, constipation, and overall abdominal
symptoms of bloating, discomfort and pain associated with IBS-C in
adults, as well as the constipation, infrequent stools, hard
stools, straining, and incomplete evacuation associated with CIC in
adults. LINZESS relieves constipation in children and adolescents
aged 6 to 17 years with functional constipation. 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. In children with functional
constipation aged 6 to 17 years, the recommended dose is 72
mcg.
LINZESS is not a laxative; it is the first medicine approved by
the FDA in a class called GC-C agonists. LINZESS contains a peptide
called linaclotide that activates 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 AbbVie co-develop and
co-commercialize LINZESS for the treatment of adults with IBS-C or
CIC. In Europe, AbbVie markets linaclotide under the brand name
CONSTELLA® for the treatment of adults with moderate to severe
IBS-C. In Japan, Ironwood's partner, Astellas, markets linaclotide
under the brand name LINZESS for the treatment of adults with IBS-C
or CIC. Ironwood also has partnered with AstraZeneca for
development and commercialization of LINZESS in China, and with
AbbVie for development and commercialization of linaclotide in all
other territories worldwide.
LINZESS Important Safety Information
INDICATIONS AND USAGE
LINZESS® (linaclotide) is indicated for the treatment of both
irritable bowel syndrome with constipation (IBS-C) and chronic
idiopathic constipation (CIC) in adults and functional constipation
(FC) in children and adolescents 6 to 17 years of age. It is not
known if LINZESS is safe and effective in children with FC less
than 6 years of age or in children with IBS-C less than 18 years of
age.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN
PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE
LINZESS is contraindicated in patients
less than 2 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.
Contraindications
- LINZESS is contraindicated in patients less than 2 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 2 years of
age. In neonatal mice, linaclotide increased fluid secretion as a
consequence of age-dependent elevated guanylate cyclase (GC-C)
agonism, which was associated with increased mortality within the
first 24 hours due to dehydration. There was no age dependent trend
in GC-C intestinal expression in a clinical study of children 2 to
less than 18 years of age; however, there are insufficient data
available on GC-C intestinal expression in children less than 2
years of age to assess the risk of developing diarrhea and its
potentially serious consequences in these patients.
Diarrhea
- In adults, 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.
- In children and adolescents 6 to 17 years of age, diarrhea was
the most common adverse reaction in 72 mcg LINZESS-treated patients
in the FC double-blind placebo-controlled trial. Severe diarrhea
was reported in <1% of 72 mcg LINZESS treated 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 or CIC adult patients: diarrhea, abdominal pain,
flatulence, and abdominal distension.
- In FC pediatric patients: diarrhea.
Please see full Prescribing Information including Boxed Warning:
https://www.rxabbvie.com/pdf/linzess_pi.pdf
LINZESS® and CONSTELLA® are registered trademarks of Ironwood
Pharmaceuticals, Inc. Any other trademarks referred to in this
press release are the property of their respective owners. All
rights reserved.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (Nasdaq: IRWD), an S&P SmallCap
600® company, is a leading gastrointestinal (GI) healthcare company
on a mission to advance the treatment of GI diseases and redefine
the standard of care for GI patients. We are pioneers in the
development of LINZESS® (linaclotide), the U.S. branded
prescription market leader for adults with irritable bowel syndrome
with constipation (IBS-C) or chronic idiopathic constipation (CIC).
LINZESS is also approved for the treatment of functional
constipation in pediatric patients ages 6-17 years-old. Ironwood is
also advancing apraglutide, a next-generation, long-acting
synthetic GLP-2 analog being developed for rare gastrointestinal
diseases, including short bowel syndrome with intestinal failure
(SBS-IF), as well as several earlier-stage assets. Building upon
our history of GI innovation, we keep patients at the heart of our
R&D and commercialization efforts to reduce the burden of GI
diseases and address significant unmet needs.
Founded in 1998, Ironwood Pharmaceuticals is headquartered in
Boston, Massachusetts, with a site in Basel, Switzerland.
We routinely post information that may be important to investors
on our website, www.ironwoodpharma.com. In addition, you can follow
us on X and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Investors are cautioned not to place undue reliance on these
forward-looking statements, including statements about the
assessment of the data from the Phase III STARS clinical trial of
apraglutide; the efficacy, safety and tolerability of apraglutide;
Ironwood’s plan to submit an NDA and marketing applications to
other regulatory filings for apraglutide and the expected timing to
complete U.S. regulatory submission; the estimated adult population
who suffer from SBS-IF in the U.S., Europe and Japan; that the
findings from the Phase III STARS clinical trial reinforce the
clinical profile of once-weekly apraglutide and confirm consistency
of treatment effect across different subgroups; and the potential
of apraglutide to be available as the first once-weekly treatment
option for patients with SBS who are dependent on PS. These
forward-looking statements speak only as of the date of this press
release, and Ironwood undertakes no obligation to update these
forward-looking statements. 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 of our products and
product candidates; the risk that clinical programs and studies,
including for products and product candidates may not progress or
develop as anticipated, including that studies are delayed or
discontinued for any reason, such as safety, tolerability,
enrollment, manufacturing, economic or other reasons; the risk that
findings from our completed nonclinical studies and clinical trials
may not be replicated in later trials and earlier-stage clinical
trials may not be predictive of the results we may obtain in
later-stage clinical trials or of the likelihood of regulatory
approval; the risk that apraglutide will not be approved by the FDA
or other regulatory agencies; the risk of competition or that new
products may emerge that provide different or better alternatives
for treatment of the conditions that our products are approved to
treat; the efficacy, safety and tolerability of linaclotide and our
product candidates; the risk that the commercial and therapeutic
opportunities for LINZESS, apraglutide or our other product
candidates are not as we expect; decisions by regulatory and
judicial authorities; the risk we may never get additional patent
protection for linaclotide, apraglutide and other product
candidates, that patents for linaclotide, apraglutide or other
products may not provide adequate protection from competition, or
that we are not able to successfully protect such patents; the risk
that the development of any of our products is not successful or
that any of our product candidates does not receive regulatory
approval or is not successfully commercialized; outcomes in legal
proceedings to protect or enforce the patents relating to our
products and product candidates, including abbreviated new drug
application litigation; and the risks listed under the heading
“Risk Factors” and elsewhere in our Annual Report on Form 10-K for
the year ended December 31, 2023, and in our subsequent Securities
and Exchange Commission filings.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20241028774728/en/
Media: Beth Calitri, 978-417-2031
bcalitri@ironwoodpharma.com Smitha Dwarakanath, 201-616-8099
smitha.dwarakanath@fleishman.com Investors: Greg Martini,
617-374-5230 gmartini@ironwoodpharma.com Matt Roache, 617-621-8395
mroache@ironwoodpharma.com
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