Ironwood announced Praliciguat phase IIa study data
Ironwood Pharmaceuticals presented additional data from an exploratory Phase IIa study of praliciguat in patients with type 2 diabetes and hypertension during an oral session at the American Diabetes Association's 78th Scientific Sessions in Orlando, Florida. Praliciguat is an oral, once-daily soluble guanylate cyclase 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. 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 diabetes and often linked to hypertension. In addition, the data suggested that praliciguat decreased levels of apolipoprotein B, a key lipid parameter that - when elevated - is associated with increased cardiac events. 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 cholesterol, the component of total cholesterol associated with long-term cardiovascular risk. 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 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.