SNF472: Mechanism of Action and Results From Clinical Trials

Smeeta Sinha; Paolo Raggi; Glenn M. Chertow


Curr Opin Nephrol Hypertens. 2021;30(4):424-429. 

In This Article


Patients with CKD and in particular patients receiving dialysis experience accelerated VC which associates with an increased risk of cardiovascular event and death. Several interventions have been undertaken aiming to ameliorate the detrimental effects of VC; however, there are no licensed treatments for this indication. The majority of interventions have focused on addressing potential etiological factors (e.g., hyperphosphatemia, hypercalcemia, secondary hyperparathyroidism) rather the final common pathway of HAP nucleation and crystal formulation. SNF472 is a first-in-class inhibitor of HAP formation which has been shown to have potent effects on inhibiting VC in vitro and in vivo. SNF472 has progressed through early phase clinical trials in healthy volunteers and patients receiving haemodialysis with a favourable safety profile. The results from the recently completed Phase 2 study showed attenuation of progression in coronary artery and aortic valve calcification at 12 months. SNF472 is also being evaluated in a Phase 3 study in calciphylaxis. A trial in PAD-ESKD is being planned. These and other studies of SNF472 should help to elucidate the role of a direct calcification inhibitor in preventing multiple complications of dystrophic calcification of ESKD.