VICTORION-Mono China: efficacy and safety of inclisiran as monotherapy in Chinese adults with low or moderate ASCVD risk and elevated LDL-C

Abstract Background Cumulative exposure to LDL-C increases the risk of ASCVD events. Despite available treatments, many Chinese patients at risk of ASCVD fail to achieve guideline-recommended LDL-C goals, often due to poor adherence and/or tolerability to lipid-lowering therapies. Twice-yearly (after initial and 3-month doses) inclisiran, an siRNA targeting PCSK9, provides effective and sustained LDL-C reduction when combined with statins and/or other lipid-lowering therapies. VICTORION-Mono China is the first study to evaluate inclisiran as monotherapy in a Chinese population. Purpose To evaluate the efficacy and safety of inclisiran as monotherapy in Chinese adults with low/moderate ASCVD risk and elevated LDL-C who are not on lipid-lowering therapy. Methods This Phase 3, multi-centre, two-part randomised trial included a double-blind, placebo-controlled 6-month treatment period and 6-month open-label period. Chinese patients aged 18–75 years, with low/moderate ASCVD risk as per Chinese guidelines, fasting LDL-C ≥130 to <190 mg/dL at screening, and not on lipid-lowering therapy, were randomised 1:1 to receive inclisiran sodium 300 mg (inclisiran 284 mg) or placebo. The primary objective was to assess the efficacy of inclisiran versus placebo on the mean percentage change in LDL-C from baseline to Day 150. Secondary objectives included absolute change in LDL-C and percentage change in other atherogenic lipids and PCSK9 at Day 150; percentage change in LDL-C at Day 330; and safety and tolerability of inclisiran. Results Overall, 207 participants were randomised to receive either inclisiran (n=103) or placebo (n=104). Mean age was 47.9 years, 58.5% were female, and mean baseline LDL-C was 149.9 mg/dL (Table). Overall, 167 patients (80.7%) had low and 37 (17.9%) had moderate ASCVD risk. Inclisiran treatment met the primary endpoint: mean placebo-adjusted percentage change in LDL-C was –47.50% (95% CI: −52.35, −42.65, p<0.0001) from baseline to Day 150. The LDL-C reduction was evident at Day 30 and was sustained through Day 360 (Figure). Absolute placebo-adjusted LDL-C change at Day 150 was −69.73 mg/dL (95% CI: −76.60, −62.86; p<0.0001). Inclisiran also lowered PCSK9 (−77.83%), total cholesterol (−31.49%), non-HDL-C (−40.57%), and apoB (−36.84%) at Day 150 (all p<0.0001). At Day 330, the mean percentage change in LDL-C was −45.45% (95% CI: −48.57, −42.34) for the inclisiran group. In the double-blinded part, adverse event rates in the inclisiran and placebo groups were similar at 70.9% (73/103) and 67.3% (70/104), respectively. Treatment-related adverse events were more frequent in the inclisiran (13.6%) than in the placebo (3.8%) group, but none were serious. No new safety signals were identified. Conclusion Inclisiran monotherapy was well-tolerated and resulted in sustained and effective reductions in LDL-C and other pro-atherogenic lipids in Chinese patients, establishing it as a potentially useful treatment option for patients at risk of ASCVD.