Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol
Summary
This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD or ASCVD-Risk equivalents and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) inclisiran injection(s). The study will be an international multicenter study (non-United States).
Timeline
- Start
- 2017-11-01
- Primary completion
- 2019-07-31
- Completion
- 2019-08-27
Outcome
Met primary endpoint
registry LEAST_SQUARES_MEAN Inclisiran: -49.3 (-51.22 to -47.48) Percent change NCT03400800 ↗
registry analysis (superiority test); Inclisiran vs Placebo; p <0.0001; Mean Difference (Final Values) -53.5 (95% CI -56.66 to -50.35); ANCOVA NCT03400800 ↗
registry LEAST_SQUARES_MEAN Inclisiran: -45.82 (-47.52 to -44.13) Percent change NCT03400800 ↗
registry analysis (superiority test); Inclisiran; p <0.0001; Mean Difference (Final Values) -49.17 (95% CI -51.57 to -46.77); ANCOVA NCT03400800 ↗
release “For the primary endpoints of ORION-11, inclisiran delivered placebo-adjusted change in LDL-C reductions of 50% ( P <.0001) at 17 months” novartis.com ↗
release “For the primary endpoints of ORION-11, inclisiran delivered placebo-adjusted change in LDL-C reductions of 50% ( P <.0001) at 17 months” novartis.com ↗
release “For the primary endpoints of ORION-11, Leqvio delivered placebo-adjusted change in LDL-C reductions of 50% ( P <.0001) at 510 days” novartis.com ↗
Publications
- Landmesser U, Ray KK, Raal FJ, Garcia Conde L, Han J, Koenig W, Leiter LA, Schwartz GG, Wright RS; on behalf of the ORION Investigators. Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials. J Am Soc Nephrol. 2026 Jul 1;37(7):1497-1506. doi: 10.1681/ASN.0000001006. Epub 2026 Jan 28.
- Wright RS, Ray KK, Landmesser U, Koenig W, Raal FJ, Leiter LA, Conde LG, Han J, Schwartz GG. Effects of Inclisiran in Patients With Atherosclerotic Cardiovascular Disease: A Pooled Analysis of the ORION-10 and ORION-11 Randomized Trials. Mayo Clin Proc. 2024 Jul 5:S0025-6196(24)00167-8. doi: 10.1016/j.mayocp.2024.03.025. Online ahead of print.
- Leiter LA, Raal FJ, Schwartz GG, Koenig W, Ray KK, Landmesser U, Han J, Conde LG, Wright RS. Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials. Diabetes Obes Metab. 2024 Aug;26(8):3223-3237. doi: 10.1111/dom.15650. Epub 2024 May 17.
- Dutta S, Shah R, Singhal S, Singh S, Piparva K, Katoch CDS. A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients. Expert Opin Drug Saf. 2024 Feb;23(2):187-198. doi: 10.1080/14740338.2023.2293201. Epub 2023 Dec 19.
- Ray KK, Wright RS. Plain language summary of results from ORION-10 and ORION-11: two studies to learn how well inclisiran works in people with high cholesterol. Future Cardiol. 2023 Mar;19(4):175-184. doi: 10.2217/fca-2022-0133. Epub 2023 Jun 6.
- Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Inclisiran | Small interfering RNA (siRNA) | 300 mg | Subcutaneous |