Table 2. Previous and ongoing trials of inclisiran.
| First Author (Year) (Ref #) | Participant number | Population | Development stage | Key findings |
|---|---|---|---|---|
| Fitzgerald et al. (2017) 37) | 69 (a single-ascending- dose phase or a multiple-dose phase, with or without concurrent statin therapy) | Participants without a history of ASCVD or diabetes who had a serum LDLC level of at least 100 mg/dL and a fasting triglyceride level of less than 400 mg/dL | Phase 1 | In the single-dose phase, inclisiran doses of 100 mg or more reduced the LDL-C level (up to a LS mean reduction of 50.6% from baseline). Reductions in the level of LDL-C was maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the level of LDL-C (up to a LS mean reduction of 59.7% from baseline to day 84). |
| Ray et al. (2017) 98) | 501 (a single or two dose) | Participants with LDL-C levels of at least 70 mg/dL for those with a history of ASCVD, or at least 100 mg/dL for those without a history of ASCVD | Phase 2 |
The ORION-1 trial showed the LS mean reductions in LDL-C levels at day 180 were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses. At day 240, LDL-C levels remained significantly lower than at baseline in association with all inclisiran regimens. |
| Raal et al. (2020) 99) | 482 | Patients with heterozygous FH | Phase 3 |
The ORION-9 trial showed that incrysilan reduced LDL-C by an average of 47.9% (95% CI: 50.5% - 45.3%) compared with placebo. |
| Ray et al. (2020) 100) |
1,561 (The ORION- 10), 1,617 (The ORION-11) |
The ORION-10 (U.S.) and ORION-11 trial (Europe and South Africa) included adults with ASCVD whose LDL-C levels were more than 70 mg/dL (1.8 nmol/L). |
Phase 3 | In the ORION-10 and ORION- 11 trial, Lp(a) had median baseline values of 57 and 42 (nmol/L), respectively, and decreased by 21.9% and 18.6%. |
| Ray et al. (2022) 38) | 3660 | The ORION-9, -10, and 11 trial pooled. | Phase 3 | Inclisiran significantly reduced MACE included non-adjudicated CV death, cardiac arrest, non-fatal MI, and fatal and non-fatal stroke. |
| Yamashita et al. (2024) 39) | 312 | Japanese patients with high CV risk and elevated LDL-C (including heterozygous FH) | Phase 2 |
Inclisiran (100, 200, 300 mg) significantly reduced LDL-C by Day 180 (p＜0.0001). The 300 mg dose showed the greatest reductions (LDL-C: 65.3%). Over 86% of patients on inclisiran achieved the JAS’s 2017 lipid management targets. |
| Ongoing | 16,124 (Inclisiran 300mg sc or a placebo) | Patients with a history of MI, ischemic stroke or PAD as evident by prior lower extremity artery revascularization or aortic aneurysm repair | Phase 3 | The ORION-4 trial expected completion in July 2026. |
| Ongoing | 345 (Inclisiran 300mg sc or a placebo) | Asian patients with ASCVD and LDL-C ≥ 70 mg/dL, or ASCVD high risk and LDL-C ≥ 100 mg/ dL) | Phase 3 | The ORION-18 trial expected completion in December 2026. |
ASCVD, atherosclerotic cardiovascular disease; CI, confidence interval; CV, cardiovascular; FH, familial hypercholesterolemia; JAS, Japanese Atherosclerosis Society; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); LS, least squares; MACE, major adverse cardiovascular events; MI, myocardial infarction; PAD, peripheral artery disease.