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ORION-8: Inclisiran shows efficacy and safety beyond six years

Posted on 30 August 2023 | Posted in ESC Congress 2023

When added to statin therapy, twice-yearly* inclisiran consistently reduces low-density lipoprotein cholesterol (LDL-C) beyond six years, according to late-breaking data presented from the ORION-8 trial – an open label extension of the ORION-9, ORION-10, ORION-11 and ORION-3 studies in which patients were followed up for between one and four years.

Of the 2,446/3,274 patients with atherosclerotic cardiovascular disease (ASCVD) or at risk of developing CV disease who completed three years of treatment in ORION-8, 78.4% (95% CI: 76.8, 80.0) reached their pre-specified LDL-C target at up to three years of follow up. Of patients with ASCVD, 79.4% reached their LDL-C goal of <1.8 mmol/L [<70 mg/dL], and of those with ASCVD risk equivalent, 74.3% reached their goal of <2.6 mmol/L [100 mg/dL]. LDL-C levels were reduced by a mean of -49.4% (95% CI: -48.3, -50.4), and this was consistent throughout the duration of the study. In the ASCVD group the reduction was -51.0% (95% CI: -52.2, -49.9), and in the ASCVD risk equivalent group it was -42.4% (95% CI: -45.0, -39.0).

Long-term safety data were consistent with previous findings, with 9.1% of patients having an adverse event (AE) related to the study drug. Severe AEs occurred in 30.2%, fatal severe AEs occurred in 5%, and AEs leading to treatment discontinuation occurred in 2.4%. Amongst those with treatment emergent adverse events (TEAEs), the most common were COVID-19 (13.8%), diabetes or inadequate control of diabetes (7.0%) and hypertension (7.0%). Of serious TEAEs, coronary artery disease (2.0%), COVID-19 (1.5%) and acute MI (1.3%) were most common. TEAEs of interest included injection site (5.9%), hepatic events (5.1%), new onset or worsening of diabetes (17.8%) and MACE (9.2%).

Dr Scott Wright (Mayo Clinic, Rochester, USA) pointed out that cumulative exposure to inclisiran in ORION-8 was over 12,000 patient years, with mean exposure of 3.7 years and longest exposure of 6.8 years.

“ORION-8 provides additional evidence to support the long term efficacy, safety and tolerability of inclisiran in patients with high cardiovascular risk and elevated LDL-cholesterol,” he concluded.

* After an initial dose and another at three months



Wright RS, Raal FJ, Koenig W et al. ORION-8: Long-term efficacy and safety of twice-yearly inclisiran in high cardiovascular risk patients. Presented at ESC Congress 2023, Amsterdam, The Netherlands (25-28 August). Late-breaking science on pharmacology.


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