Cyclerion announced top-line data from its Phase II proof-of-concept trial of praliciguat in diabetic nephropathy and the CAPACITY trial praliciguat in heart failure with preserved ejection fraction (HFpEF). Neither trial met statistical significance on its primary endpoint.
The CAPACITY study was a randomized, placebo-controlled study and evaluated the safety and efficacy of once-daily praliciguat 40 mg or placebo in 196 patients with HFpEF over a 12-week period. The study did not meet statistical significance on its primary endpoint of improved exercise capacity from baseline as compared to placebo, measured by cardiopulmonary exercise testing (CPET). There was clear evidence of drug exposure and pharmacological activity as judged by expected reductions in blood pressure. Praliciguat was generally well tolerated and had a good safety profile. Based on these results, the company is discontinuing the development of praliciguat in HFpEF.
The phase 2 diabetic nephropathy study was a randomized, placebo-controlled, dose-ranging design and evaluated the safety and efficacy of once-daily praliciguat 20 mg, praliciguat 40 mg or placebo in 156 patients with diabetic nephropathy over a 12-week period. The study did not meet statistical significance on its primary endpoint of reduction in albuminuria from baseline as compared to placebo, measured by urine albumin creatinine ratio (UACR), but there was a trend toward improvement across the total intention-to-treat (ITT) study population. In addition, improvements were observed in patients treated with praliciguat in several secondary vascular and metabolic measures associated with cardiovascular risk and kidney disease progression, including blood pressure, cholesterol and HbA1c levels, compared to placebo. Based on these positive trends on primary and secondary endpoints plans to further investigate praliciguat in this indication.
The company intends to pursue an out-license of praliciguat for late-stage development.
Praliciguat is an orally administered, once-daily systemic sGC stimulator designed for the treatment of serious cardiometabolic diseases such as Diabetic Nephropathy, or DN, and Heart Failure with Preserved Ejection Fraction, or HFpEF. In a preclinical study, oral praliciguat demonstrated extensive distribution to adipose tissue, kidney, heart, and liver, and the extensive distribution of praliciguat has been confirmed in clinical studies.