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ORION-8 is the largest study on LEQVIO® to date1
ORION-8 provides additional evidence to support the long-term efficacy and safety profile of LEQVIO® in patients with ASCVD and elevated LDL-C with up to 6.8 years of treatment.1
The effect of inclisiran on cardiovascular morbidity and mortality has not yet been determined.2,3
- With a baseline LDL-C of 2.92 mmol/L (± 1.2), nearly 80% of patients with ASCVD achieved the 1.8 mmol/L LDL-C target1
- On average LDL-C levels were reduced by ~50% from baseline in eligible patients with ASCVD on LEQVIO® and the maximally tolerated statin, which is consistent with the Phase III trials ORION-9, ORION-10 and ORION-111,4–6
- The mean cumulative exposure to LEQVIO® in ORION-8 was 3.7 years with a maximum of 6.8 years, providing a total of >12,000 patient-years of exposure1
The safety profile of LEQVIO® remains consistent with that previously reported, with no additional safety signals identified beyond 6 years of treatment.1
ORION-8 provides additional evidence to support the long-term efficacy and safety profile of LEQVIO® in patients with ASCVD and elevated LDL-C beyond 6 years of treatment:1
Primary endpoints:1
- Proportion of patients achieving pre-specified LDL-C goals at the end of the study*
- Pre-specified lipid goals: ASCVD <1.8 mmol/L (<70 mg/dL); ASCVD risk equivalent <2.6 mmol/L (<100 mg/dL)
- Safety profile
Secondary endpoint:1
- Percentage change in LDL-C from baseline to end of the study*
Study design:1
The recommended dose is 284 mg of inclisiran administered as a single subcutaneous injection: initially, again at 3 months, followed by every 6 months.2,3
ORION-8 provides additional evidence to support the long-term efficacy and safety profile of LEQVIO® in patients with ASCVD and elevated LDL-C beyond 6 years of treatment:1
The table below provides you with a summary of the safety data from the ORION-8 trial.
| Category | Total (N=3274) n (%) |
| AEs | 2548 (77.8) |
| AEs related to study drug | 297 (9.1) |
| SAEs | 989 (30.2) |
| Fatal SAEs | 165 (5.0) |
| AEs leading to study treatment discontinuation | 80 (2.4) |
| TEAEs occurring in ≥3% patients | |
| Total (N=3274) n (%) | |
| Patients with at least one TEAE | 2548 (77.8) |
| COVID-19 | 453 (13.8) |
| Diabetes mellitus inadequate control | 229 (7.0) |
| Hypertension | 229 (7.0) |
| Diabetes mellitus | 206 (6.3) |
| Arthralgia | 205 (6.3) |
| Urinary tract infection | 158 (4.8) |
| Osteoarthritis | 149 (4.6) |
| Back pain | 131 (4.0) |
| Nasopharyngitis | 110 (3.4) |
| Upper respiratory tract infection | 110 (3.4) |
| Atrial fibrillation | 100 (3.1) |
| Coronary artery disease | 99 (3.0) |
| Serious TEAEs occurring in ≥1% patients | |
| Total (N=3274) n (%) | |
| Patients with at least one serious TEAE | 989 (30.2) |
| Coronary artery disease | 64 (2.0) |
| COVID-19 | 49 (1.5) |
| Acute myocardial infarction | 44 (1.3) |
| Angina pectoris | 43 (1.3) |
| Osteoarthritis | 36 (1.1) |
| Atrial fibrillation | 35 (1.1) |
| Pneumonia | 35 (1.1) |
| COVID-19 pneumonia | 35 (1.1) |
| Death | 33 (1.0) |
| Myocardial infarction | 33 (1.0) |
You can proactively look for patients who are eligible to start LEQVIO® in both primary and secondary care
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*End of study was either Day 1080 or ≥90 days following the last dose of LEQVIO®.1
†The ORION-3 trial was an open-label extension of the Phase II ORION-1 trial (1 year).7
‡One LEQVIO® patient in ORION-9/10/11 did not receive any injection in ORION-8.1
§Reasons for not completing the 3 years of treatment included: sponsor’s administrative decision for the roll-over ORION-3 patients only (8.31%), death (5.04%), withdrawal of consent (4.80%) and loss to follow-up mostly during the COVID-19 pandemic period (3.05%), other (2.72%) and adverse events (1.37%).1
¶Patients from ORION-3 did not receive any drug administration on Day 1. Only patients on placebo in the feeder trials received an active LEQVIO® injection at Day 1; patients who received LEQVIO® in those trials received blinded placebo at this visit.1
AE, adverse event; ASCVD, atherosclerotic cardiovascular disease; COVID-19, coronavirus disease 2019; D, day; ESC, European Society of Cardiology; LDL-C, low-density lipoprotein cholesterol; SAE, serious adverse event; TEAE, treatment-emergent adverse event.
References
- Wright RS, et al. Oral presentation. ORION-8: Long-term efficacy and safety of twice-yearly inclisiran in high cardiovascular risk patients. ESC Congress 2023. Amsterdam, The Netherlands, 25–28 August 2023.
- LEQVIO® Great Britain. Summary of Product Characteristics.
- LEQVIO® Northern Ireland. Summary of Product Characteristics.
- Raal FJ, et al. N Engl J Med 2020;382:1520–1530.
- Ray KK, et al. N Engl J Med 2020;382:1507–1519.
- Ray KK, et al. Eur Heart J 2022;43(48):5047–5057.
- Ray KK, et al. Lancet Diabetes Endocrinol 2023;11(2):109–119.
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