Three placebo-controlled phase 3 trials have evaluated the efficacy and safety of inclisiran. Inclisiran lowered low-density lipoprotein (LDL) cholesterol similarly across all ages with an acceptable safety profile . The efficacy and safety profile of inclisiran was generally similar in both sexes .
Prof. R. Scott Wright (Mayo Clinic, USA) presented the results of 2 pooled analyses evaluating the efficacy and safety of inclisiran according to age and sex, respectively. Both analyses included data from three phase 3 placebo-controlled trials:
- ORION-9 in patients with heterozygous familial hypercholesterolaemia (HeFH);
- ORION-10 in patients with atherosclerotic cardiovascular disease (ASCVD); and
- ORION-11 in patients with ASCVD or ASCVD risk equivalents.
In the first analysis, a total of 3,660 patients were categorised according to age: <65 years (not old; n=1,737), 65 to <75 years (old; n=1,431), or ≥75 years (very old; n=492) . After 18 months (540 days) of follow-up, the placebo-corrected change in LDL cholesterol with inclisiran was around 50% in not old, old, and very old patient groups: −51.3%, −49.9%, and −51.0%, respectively (P<0.0001 from baseline for all). The co-primary endpoint of time-adjusted change in LDL cholesterol from baseline to day 90 up to day 540 yielded very similar results: −49.6%, −51.5%, and −50.8% (P<0.0001 for all). Rates of adverse events (AE) and serious AE increased with age and were similar to placebo in all groups, with the exception of injection-site reactions, which were higher with inclisiran across all ages.
The second analysis found a similar efficacy of inclisiran for both primary endpoints in men (67.5%; n=2,470) and women (32.5%; n=1,190). Women had higher LDL cholesterol at baseline: 122.9 versus 105.8 mg/dL. Placebo-corrected mean absolute reduction in LDL cholesterol at day 510 was also higher in women (62.6 vs 54.0 mg/dL), as was time-adjusted reduction from days 90 to 540 (59.0 vs 51.5 mg/dL) (both P<0.05). Safety of inclisiran was generally similar in both sexes, again except for injection-site AEs, which were more frequent compared with placebo, more frequent in women (women 9.4% vs 0.2%, men 2.8% vs 0.9%), and generally mild.
- Wright RS, et al. Efficacy and Safety of Inclisiran According to Age: A Pooled Analysis of Phase III Studies (ORION 9, 10 and 11). P2250, AHA Scientific Sessions 2020, 13–17 Nov.
- Wright RS, et al. Efficacy and Safety of Inclisiran According to Sex: A Pooled Analysis of the ORION 9, 10 and 11 Trials. P2253, AHA Scientific Sessions 2020, 13–17 Nov.
« Remote risk management programme effective and efficient Next Article
No CV benefit from omega 3 in high-risk patients »