– Data provide additional evidence supporting
development of praliciguat as a potential treatment for diabetic
nephropathy and for heart failure with preserved ejection fraction
–
Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD), a commercial
biotech company, today presented additional data from an
exploratory Phase IIa study of praliciguat (IW-1973) in patients
with type 2 diabetes and hypertension during an oral session at the
American Diabetes Association’s (ADA) 78th Scientific Sessions
in Orlando, Fla. Praliciguat is an oral, once-daily soluble
guanylate cyclase (sGC) stimulator that is currently being studied
in Phase II clinical trials in patients with diabetic nephropathy
and in patients with heart failure with preserved ejection fraction
(HFpEF).
Building on previously announced top-line data from the Phase
IIa randomized, placebo-controlled, 14-day study, which showed that
treatment with praliciguat led to reductions in blood pressure,
fasting plasma glucose, cholesterol levels and triglycerides in
patients on a stable regimen of medicines to manage their disease,
the newly reported findings also suggested that praliciguat
improved insulin sensitivity. Insulin resistance is a hallmark of
diabetes1 and often linked to hypertension2. In addition, the data
suggested that praliciguat decreased levels of apolipoprotein B
(ApoB), a key lipid parameter that – when elevated – is associated
with increased cardiac events3. The effect of praliciguat on ApoB
in this Phase IIa study was shown within the context of broader
lipid effects, including a reduction in total cholesterol and
low-density lipoprotein (LDL) cholesterol, the component of total
cholesterol associated with long-term cardiovascular risk.
“In this study, praliciguat demonstrated a positive impact
across critical biomarkers of metabolic and cardiovascular disease
– including blood pressure, lipids, and glucose – providing a
strong rationale for praliciguat as a potential treatment for
diabetic nephropathy and for HFpEF,” said Christopher Wright, M.D.,
Ph.D., senior vice president, global development and chief
development officer at Ironwood. “We’re advancing our Phase II
programs for these diseases, which both impact millions of patients
worldwide, have limited treatment options and are associated with
serious long-term consequences including organ failure and
death.”
The newly disclosed data presented at the ADA Scientific
Sessions were as follows:
- Improvement in insulin
sensitivity: In patients treated with praliciguat who were not
taking concomitant insulin, Homeostatic Model Assessment of Insulin
Resistance (HOMA-IR) score – a measure of insulin resistance –
declined by an average of 36% from baseline to day 15, following
completion of the study treatment regimen, compared to a decrease
of 13% in patients taking placebo, representing a 23% greater
reduction with praliciguat compared to placebo.
- Decline in ApoB: Patients
treated with praliciguat showed a mean decrease in ApoB of 170
mcg/ml from baseline to day 15, compared to a decrease of 51 mcg/ml
in patients taking placebo, a 119 mcg/ml greater reduction with
praliciguat compared to placebo.
The Phase IIa exploratory study was designed to evaluate the
safety, tolerability, pharmacokinetics and pharmacodynamics of
praliciguat in diabetic patients with hypertension, and included a
number of exploratory biomarkers related to diabetes and
cardiovascular disease. 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
data were combined for analysis.
The study was not designed or powered to assess efficacy, but
the data yielded clear and consistent trends indicating a positive
effect of praliciguat on blood pressure, metabolic parameters and
endothelial function biomarkers. These improvements were seen in
patients who were taking a stable regimen of therapies to manage
their disease; all participating patients were taking at least one
medication to manage their hypertension and at least one medication
to manage their diabetes, and a majority were also taking
additional medications to manage their cholesterol and serum lipid
levels. The study also confirmed a pharmacokinetic profile of
praliciguat supporting once-daily dosing and suggested broad
distribution to relevant tissues, offering the potential to
maximize anti-inflammatory, anti-fibrotic and metabolic
effects.
Praliciguat was generally well-tolerated. Nausea was the only
adverse event (AE) present in the praliciguat 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 praliciguat. Across all five clinical studies
of praliciguat to date, praliciguat was found not to impair
platelet function or blood clotting, either on its own or when
co-administered with aspirin. No other serious bleeding episodes
have been observed. All other AEs in this Phase IIa study were
characterized as mild.
About Praliciguat
Praliciguat (IW-1973), an oral, once-daily 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, praliciguat 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 praliciguat (IW-1973) for the potential
treatment of diabetic nephropathy and of heart failure with
preserved ejection fraction (HFpEF). Olinciguat (IW-1701) is being
developed for the potential treatment of achalasia and of sickle
cell disease. In addition, Ironwood has a pipeline of other sGC
stimulators in pre-clinical 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 to
be taken with a xanthine oxidase inhibitor (XOI), or as a
fixed-dose combination with allopurinol, for the treatment of
hyperuricemia associated with gout. We are also advancing a
pipeline of innovative product candidates in areas of significant
unmet need, including persistent 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.
Forward-Looking Statements
This press release contains forward-looking statements.
Investors are cautioned not to place undue reliance on these
forward-looking statements, including statements about Ironwood's
sGC program and the clinical program for praliciguat; the
assessment of the data from the clinical trials of praliciguat; the
mechanism of action of praliciguat; prevalence and unmet need; the
development, regulatory and commercialization plans for
praliciguat; and praliciguat as a potential treatment for diabetic
nephropathy and HFpEF. 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 praliciguat; the risk that the therapeutic
opportunities for praliciguat are not as we expect; decisions by
regulatory authorities; the risk that we may never get sufficient
patent protection for praliciguat or that we are not able to
successfully protect such patents; the outcomes in legal
proceedings to protect or enforce the patents relating to
praliciguat; 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 business or the praliciguat program; and those risks
listed under the heading "Risk Factors" and elsewhere in Ironwood's
Quarterly Report on Form 10-Q for the quarter ended March 31, 2018,
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 “Insulin Sensitivity.” Diabetes.co.uk.
https://www.diabetes.co.uk/insulin/insulin-sensitivity.html.
Accessed June 14, 2018.2 Salvetti A, Brogi G, Di Legge V, Bernini
GP. (1993). The inter-relationship between insulin resistance and
hypertension. Drugs. 1993;46 Suppl 2:149-59.
https://www.ncbi.nlm.nih.gov/pubmed/75124683 Walldius, G., &
Junger, I. (2004). Apolipoprotein B and apolipoprotein A-I: risk
indicators of coronary heart disease and targets for
lipid-modifying therapy. Journal of Internal Medicine, 255(2),
188-205. https://www.ncbi.nlm.nih.gov/pubmed/14746556
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version on businesswire.com: https://www.businesswire.com/news/home/20180623005031/en/
Media and Investors:Ironwood PharmaceuticalsMeredith
Kaya, 617-374-5082Vice President, Investor Relations and Corporate
Communicationsmkaya@ironwoodpharma.comorJessi Rennekamp,
617-374-5404Associate Director, Corporate
Communicationsjrennekamp@ironwoodpharma.com
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