– Addition of IW-1973 to ongoing medical
regimens used to treat diabetic patients with hypertension showed
reductions in blood pressure, fasting plasma glucose, cholesterol
and triglycerides, and improved endothelial function –
–Data support advancement of IW-1973 for
evaluation as a potential treatment for patients with diabetic
nephropathy and for patients with heart failure with preserved
ejection fraction –
Ironwood Pharmaceuticals, Inc. (NASDAQ:IRWD) today
announced encouraging top-line results from two Phase IIa studies
of IW-1973, Ironwood’s lead investigational soluble guanylate
cyclase (sGC) stimulator, in patients with type 2 diabetes and
hypertension. Consistent with pre-clinical observations, in both
studies treatment with IW-1973 led to blood pressure reductions and
improvements in metabolic parameters, including reductions in
fasting plasma glucose and cholesterol levels, in patients who were
taking a stable regimen of therapies to manage their disease.
Elevated levels of plasma cGMP provided clear evidence of target
engagement. These studies confirm a pharmacokinetic profile of
IW-1973 supporting once-daily dosing and suggest broad distribution
to tissues, offering the potential for extra-vascular pharmacology.
IW-1973 was generally well-tolerated.
Ironwood is currently developing IW-1973 for the treatment of
diabetic nephropathy and for the treatment of heart failure with
preserved ejection fraction (HFpEF). The company recently initiated
two new Phase II dose-ranging clinical trials with IW-1973 in these
indications.
“We are encouraged by the pharmacokinetic profile of IW-1973
that supports a once-daily dosing regimen, as well as its safety
and tolerability profile, as observed in the Phase IIa studies,”
said Christopher Wright, MD, PhD, senior vice president of global
development and chief development officer at Ironwood. “In
addition, we are excited to see signals of a positive impact of
IW-1973 on vascular and metabolic biology important to diabetes and
heart failure, particularly since they were observed on top of
existing therapies. These data further reinforce our commitment to
developing IW-1973 in patients with diabetic nephropathy and in
patients with HFpEF, two diseases of significant unmet need
estimated to affect millions of patients around the world, and we
are advancing our ongoing larger Phase II trials in these
indications.”
The two Phase IIa exploratory studies were designed to evaluate
the safety and tolerability, pharmacokinetics and pharmacodynamics
of IW-1973 in diabetic patients with hypertension on a stable
regimen of medicines to manage their disease. The studies were not
designed or powered explicitly to assess efficacy, but the data
yielded clear and consistent trends indicating a positive effect of
IW-1973 on blood pressure, metabolic parameters and endothelial
function biomarkers.
The larger of the two exploratory studies (n=26) was a
randomized, placebo-controlled, 14-day study. Participating
patients were required to remain on their existing treatment
regimens. All were taking at least one medication to manage their
hypertension and at least one medication to manage their diabetes;
a majority were also taking additional medications to manage their
cholesterol and serum lipid levels. Approximate mean baseline
pre-treatment characteristics of the study participants were mean
arterial blood pressure of 92 mmHg, fasting plasma glucose of 150
mg/dL, serum cholesterol of 156 mg/dL and serum triglycerides of
153 mg/dL. The study included two active dosing regimens: (1) 40 mg
once-daily for days 1 to 14, and (2) 20 mg twice daily for days 1
to 7 followed by 40 mg once-daily for days 8 to 14. Overall results
were similar for both dosing regimens and were combined. Top-line
data were as follows:
- Decrease in Blood Pressure: At
day 14, patients treated with IW-1973 showed a mean decrease in
mean arterial blood pressure of 6.3 mmHg from baseline compared to
a decrease of 1.6 mmHg from baseline in patients treated with
placebo, as measured by 24-hour ambulatory blood pressure
monitoring (ABPM), which was a 4.7% greater reduction in patients
treated with IW-1973 compared to placebo-treated patients.
- Decrease in Fasting Glucose: At
day 15, following completion of the study treatment regimen,
patients treated with IW-1973 showed a mean decrease in fasting
plasma glucose of 32.5 mg/dL from baseline compared to a decrease
of 19.7 mg/dL from baseline in patients treated with placebo, which
was a 10% greater reduction in patients treated with IW-1973
compared to placebo-treated patients.
- Decrease in Cholesterol: At day
15, patients treated with IW-1973 showed a mean decrease in serum
cholesterol of 24.7 mg/dL from baseline compared to an increase of
0.8 mg/dL from baseline in patients treated with placebo, which was
a 15.4% greater reduction in patients treated with IW-1973 compared
to placebo-treated patients. The reduction was largely attributable
to a decrease in low-density lipoprotein (LDL), the component of
total cholesterol associated with long-term cardiovascular
risk.
- Decrease in Triglycerides: At
day 15, patients treated with IW-1973 showed a mean decrease in
serum triglycerides of 46.2 mg/dL from baseline compared to a
decrease of 32.0 mg/dL from baseline in patients treated with
placebo, which was a 14.4% greater reduction in patients treated
with IW-1973 compared to placebo-treated patients.
- Reduction in Biomarker of
Endothelial Dysfunction: Levels of asymmetric dimethylarginine
(ADMA), a key biomarker for endothelial dysfunction and
cardiovascular risk, were reduced from baseline in patients
receiving IW-1973 compared to patients receiving placebo.
The most common adverse events (AE) reported in patients treated
with IW-1973 were headache, hypoglycemia and nausea. Only nausea
was present in the IW-1973 group at a greater incidence rate than
placebo. There was a single serious AE, an upper gastrointestinal
hemorrhage in a participant with erosive esophagitis receiving
IW-1973. All other AEs were characterized as mild.
The second, smaller trial (n=11) was an open-label, rapid dose
escalation study. Results from this study were similar to those in
the 14-day, randomized, placebo-controlled trial, including
reductions in blood pressure, fasting plasma glucose, cholesterol
and triglyceride levels, and ADMA levels. The most common AE
reported was headache. All AEs were characterized as mild or
moderate.
About IW-1973
IW-1973, Ironwood’s lead soluble guanylate cyclase (sGC)
stimulator, is being studied in patients with diabetic nephropathy
and in patients with heart failure with preserved ejection fraction
(HFpEF). Diabetic nephropathy affects an estimated eight million
Americans and 20 to 40 percent of all diabetic patients worldwide.
It is the leading cause of end-stage renal disease. Currently
available products do not treat the underlying pathophysiology of
the disease or fully address the needs of this patient population.
HFpEF affects an estimated three million Americans and 40 to 70
percent of heart failure patients worldwide. It is a highly
symptomatic condition with high rates of morbidity and mortality
that can cause insufficient delivery of oxygen to the tissues,
fluid in the lungs and edema of the extremities, causing patients
to be short of breath and have compromised exercise tolerance.
There are no approved therapies to treat HFpEF.
Currently in Phase II development for diabetic nephropathy and
for HFpEF, IW-1973 has the potential to address the underlying
causes of these devastating diseases by improving nitric oxide (NO)
signaling, which may improve vascular and metabolic function and
decrease the inflammatory and fibrotic consequences associated with
these diseases.
About Ironwood’s sGC Program
As a pioneering expert in cyclic GMP (cGMP), Ironwood is
building on its success with linaclotide, which stimulates
guanylate cyclase-C in the intestine, to develop a pipeline of
soluble guanylate cyclase (sGC) stimulators. sGC plays an important
role in regulating diverse physiological processes; dysregulation
of sGC may play a role in multiple serious diseases. Ironwood’s sGC
stimulators are believed to harness the nitric oxide (NO)/sGC/cGMP
pathway by working synergistically with NO to improve blood flow
and metabolism and decrease inflammation and fibrosis.
Ironwood is advancing IW-1973, its lead sGC stimulator, for the
potential treatment of diabetic nephropathy and the potential
treatment of heart failure with preserved ejection fraction
(HFpEF). Ironwood’s second clinical sGC stimulator, IW-1701, is
being developed for the potential treatment of achalasia and sickle
cell disease. In addition, Ironwood has a rich pipeline of other
promising sGC stimulators in preclinical development.
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 for
the treatment of hyperuricemia associated with gout in patients who
have not achieved target serum uric acid (sUA) levels with a
medically appropriate daily dose of a xanthine oxidase inhibitor
(XOI) alone. We are also advancing a pipeline of innovative product
candidates in areas of significant unmet need, including
uncontrolled gastroesophageal reflux disease, diabetic nephropathy,
heart failure with preserved ejection fraction, achalasia and
sickle cell disease. 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.
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 clinical trials of IW-1973,
including a dosing regimen, safety, and tolerability; the
development, regulatory and commercialization plans for IW-1973,
and the timing thereof, including further investigation and
advancement of IW-1973; the design, potential indications for, and
possible benefits of IW-1973 and its potential as a treatment for
patients; prevalence and unmet need; and market size, growth and
opportunity. 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 IW-1973; the risk
that the therapeutic opportunities for IW-1973 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 IW-1973 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, 2017, 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.
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version on businesswire.com: http://www.businesswire.com/news/home/20171204005253/en/
Investor and Media RelationsIronwood Pharmaceuticals,
Inc.Meredith Kaya, 617-374-5082Senior Director, Investor Relations
and Corporate Communicationsmkaya@ironwoodpharma.com
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