Inclisiran Effective Across Kidney Function Levels, study finds

Lowering low-density lipoprotein cholesterol (LDL cholesterol) reduces the risk of atherosclerotic cardiovascular disease in patients with chronic kidney disease (CKD). The efficacy and safety of inclisiran versus placebo in patients without and with CKD were investigated in a post hoc pooled analysis of three Phase 3 trials (ORION-9, ORION-10, ORION-11). Patients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease or its risk equivalent, and elevated LDL cholesterol were randomized 1:1 to subcutaneous inclisiran or placebo on days 1, 90, and every six months thereafter for 540 days. Patients were stratified based on baseline estimated glomerular filtration rate (eGFR by Chronic Kidney Disease Epidemiology Collaboration equation): ≥90, 60–˂90, 45–˂60, and 15–<45 mL/min/1.73m2. Co-primary endpoints were percentage change in LDL cholesterol at day 510, and time-adjusted percentage change after day 90 and through day 540. Safety was also evaluated.

Results: Of 3660 patients, 1610 (44%) had eGFR ≥90, 1608 (44%) 60–˂90, 300 (8%) 45–˂60 and 142 (4%) 15–<45 mL/min/1.73 m2. Mean (95%CI) placebo-corrected percentage changes in LDL cholesterol from baseline at Day 510 in patients with eGFR ≥90, 60–˂90, 45–˂60 and 15–<45 mL/min/1.73 m2 were −49.9% (−53.2, −46.6), −51.2% (−54.4, −48.0), −54.7% (−62.5, −47.0), and −44.7% (−57.6, −31.8), respectively (P<0.001); the corresponding mean (95%CI) time-adjusted placebo-corrected percentage changes in LDL cholesterol from baseline after Day 90 through to Day 540 were −48.4% (−50.8, −46.1), −51.8% (−54.2, −49.4), −55.6% (−61.0, −50.2), and −50.4% (−59.3, −41.5), (each P<0.001). Significant decreases in total cholesterol, apolipoprotein B, non−high-density lipoprotein cholesterol, and lipoprotein(a) occurred in all eGFR groups. Inclisiran was well tolerated without new safety findings.

Inclisiran demonstrated sustained and effective LDL cholesterol reduction in patients with or at risk of atherosclerotic cardiovascular disease, regardless of baseline eGFR as low as 15 mL/min/1.73m2, without new safety findings.

Reference:

Landmesser, Ulf1,a; Ray, Kausik K.2; Raal, Frederick J.3; Conde, Lorena Garcia4; Han, Jackie5; Koenig, Wolfgang6; Leiter, Lawrence A.7; Schwartz, Gregory G.8; Wright, R. Scott9; on behalf of the ORION Investigators. Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials. Journal of the American Society of Nephrology ():10.1681/ASN.0000001006, January 28, 2026. | DOI: 10.1681/ASN.0000001006

Keywords:

Inclisiran, Effective, Across, Kidney, Function, Levels, study, finds, Landmesser, Ulf; Ray, Kausik K; Raal, Frederick J.; Conde, Lorena Garcia4; Han, Jackie; Koenig, Wolfgang, Journal of the American Society of Nephrology