Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)
Summary
This is a Phase III, placebo-controlled, double-blind, randomized study in participants with HeFH and elevated LDL-C to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) injection(s) of inclisiran. The study will be multicenter and international.
Timeline
- Start
- 2017-11-28
- Primary completion
- 2019-08-27
- Completion
- 2019-09-17
Outcome
Met primary endpoint
registry LEAST_SQUARES_MEAN Inclisiran: -41.15 (-44.52 to -37.77) percent change NCT03397121 ↗
registry analysis (superiority test); Inclisiran vs Placebo; p <.0001; Mean Difference (Final Values) -49.52 (95% CI -55.04 to -43.99) NCT03397121 ↗
registry LEAST_SQUARES_MEAN Inclisiran: -38.08 (-41.03 to -35.14) percent change NCT03397121 ↗
registry analysis (superiority test); Inclisiran vs Placebo; p <0.0001; Mean Difference (Final Values) -44.30 (95% CI -48.48 to -40.12) NCT03397121 ↗
release “ORION-9: met all primary and secondary efficacy endpoints” novartis.com ↗
release “For the primary endpoints of ORION-9, inclisiran delivered mean placebo-adjusted percentage change in LDL-C reductions of 48% ( P <.0001) at 17 months” novartis.com ↗
release “For the primary endpoints of ORION-9, inclisiran delivered mean placebo-adjusted percentage change in LDL-C reductions of 48% ( P <.0001) at 17 months” novartis.com ↗
release “For the primary endpoints of ORION-9, Leqvio delivered mean placebo-adjusted percentage change in LDL-C reductions of 48% ( 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.
- 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.
- Raal FJ, Kallend D, Ray KK, Turner T, Koenig W, Wright RS, Wijngaard PLJ, Curcio D, Jaros MJ, Leiter LA, Kastelein JJP; ORION-9 Investigators. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Apr 16;382(16):1520-1530. doi: 10.1056/NEJMoa1913805. Epub 2020 Mar 18.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Inclisiran | Small interfering RNA (siRNA) | 300 mg | Subcutaneous |