Efficacy and safety of inclisiran based on background lipid-lowering treatment

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Clinical Trials

Background:

• Atherosclerotic cardiovascular disease (ASCVD) management often involves multiple lipid-lowering therapies (LLTs).
• Understanding the efficacy of novel agents like inclisiran across different LLT backgrounds is crucial for optimizing patient care.
• Inclisiran is a small interfering RNA (siRNA) targeting PCSK9 synthesis.

Purpose of the Study:

• To assess if the LDL-C lowering effect of inclisiran differs based on patients' existing lipid-lowering therapy.
• To evaluate inclisiran's efficacy in diverse patient populations undergoing various LLT regimens.

Main Methods:

• A pooled post hoc analysis of the Phase 3 ORION-10 and ORION-11 trials (N=3178) involving patients with ASCVD or risk equivalents.
• Patients were randomized to receive inclisiran or placebo, with stratification based on baseline LLT: combination therapy (statin + ezetimibe), monotherapy (statin or ezetimibe), or no LLT.
• Relative and absolute changes in low-density lipoprotein cholesterol (LDL-C) were analyzed over a 540-day period.

Main Results:

• Inclisiran demonstrated significant and sustained LDL-C reduction across all background LLT groups.
• Mean placebo-corrected percentage reductions in LDL-C ranged from -43.1% to -57.0% from Day 90 to Day 540.
• Absolute LDL-C reductions ranged from -1.3 mmol/L to -1.7 mmol/L, irrespective of baseline LLT.

Conclusions:

• Inclisiran provides consistent and effective LDL-C lowering in patients with ASCVD, regardless of their background lipid-lowering therapy.
• The safety profile of inclisiran remained consistent across all evaluated LLT combinations.
• These findings support the use of inclisiran as a valuable therapeutic option in a broad range of ASCVD patients.