Praliciguat Soluble guanylate cyclase activator Treatment of heart failure with preserved ejection fraction Treatment of diabetic nephropathy

Disruption in the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway due to endothelial damage may play a role in the pathogenesis of chronic heart failure (HF) with preserved ejection fraction (HFpEF) and diabetic nephropathy (DN). HF is defined as a chronic progressive condition in which the heart is unable to pump an adequate volume of blood to meet the necessities of the body. Two major types of HF prevail: HF with reduced ejection fraction (HFrEF) and HFpEF. HFrEF has numerous approved therapies to reduce morbidity and mortality, while HFpEF does not have any approved therapies with such demonstrated benefits and remains a large unmet need in the United States. In relation to ON, about 40% of patients with diabetes develop this complication which can progress to end-stage renal disease (ESRD) and/or need for renal transplant. Treatment with neurohumoral antagonists is used in addition to antidiabetic therapies to slow the progression of DN in patients with proteinuria. Nevertheless, the risk of progression to ESRD still remains high and better treatment options are necessary. Praliciguat (IW-1973), a novel sGC stimulator, may have a potential therapeutic effect in chronic HFpEF and DN as it directly stimulates sGC and increases the production of endogenous cGMP.