SNF472 slows CAC progression in haemodialysis patients

SNF472 treatment resulted in a significantly slower progression of coronary artery calcium (CAC) in patients with end-stage renal disease (ESRD) receiving haemodialysis, according to a prespecified subgroup analysis of the CaLIPSO* study presented at ERA-EDTA 2020.

“SNF472 is an intravenous formulation of myo-inositol hexaphosphate … It selectively inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the development of vascular calcification,” said lead author Professor Paolo Raggi from Mazankowski Alberta Heart Institute in Edmonton, Canada.

This trial involved 274 patients (mean age 63.5 years, 39.0 percent female) with ESRD undergoing dialysis for ≥6 months who had a CAC Agatston score of 100–3,500 at baseline. Patients were randomized to receive intravenous infusion of SNF472 600 mg (n=91) or 300 mg (n=92) or placebo (n=91) three times a week for 52 weeks during dialysis sessions. [ERA-EDTA 2020, abstract SO086]

At week 52, patients in both the SNF472 dose groups combined experienced a significantly slower progression of CAC volume from baseline compared with the placebo group in the modified ITT (mITT) population (mean change in CAC volume score, 11.0 percent vs 20.0 percent; p=0.016).

In the per-protocol population comprising 160 patients who received ≥80 percent of the study drug, SNF472 recipients had a significantly slower progression of CAC volume compared with placebo recipients at 52 weeks (mean change in CAC volume score, 8.0 percent vs 24.0 percent; p<0.001). “[This] was even greater and more marked [than the mITT population],” Raggi noted.

Across all prespecified patient subgroups**, there was an overall trend towards a slower progression of CAC volume in the SNF472 arm than in the placebo arm (11.0 percent vs 20.0 percent for both mITT and per-protocol populations).

Both the SNF472 and the placebo groups showed no significant differences with regard to the treatment-emergent adverse events and composite safety endpoints. However, deaths occurred in 7 percent, 1 percent, and 6 percent of the patients in the SNF472 (for 600 and 300 mg) and placebo arms, respectively.

Raggi acknowledged that one limitation of the study was that the enrolled patients had pre-existing CAC and they could not determine whether SNF472 prevents the initial development of CAC.

“[In conclusion,] SNF472 treatment for 52 weeks [significantly] attenuated CAC progression compared with placebo … The result was consistent in all prespecified patient subgroups receiving maintenance haemodialysis,” Raggi said.

“As the trial was not designed to test whether SNF472 reduces the frequency of cardiovascular events, … further studies are needed to determine if SNF472 will lead to a decrease in risk of cardiovascular events in patients receiving haemodialysis,” he added.

*CaLIPSO: Effect of SNF472 on progression of cardiovascular calcification in end-stage-renal-disease (ESRD) patients on hemodialysis (HD)