- 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 -
CAMBRIDGE, Mass.--(BUSINESS WIRE)--
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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171204005253/en/
Investor and Media Relations
Ironwood Pharmaceuticals, Inc.
Meredith
Kaya, 617-374-5082
Senior Director, Investor Relations and
Corporate Communications
mkaya@ironwoodpharma.com
Source: Ironwood Pharmaceuticals, Inc.
News Provided by Acquire Media