What percentage of patients with statin (HMG-CoA reductase inhibitors) intolerance taking Leqvio (inclisiran) experience no change in Low-Density Lipoprotein (LDL) cholesterol levels?

Percentage of Statin-Intolerant Patients with No LDL Change on Leqvio (Inclisiran)

Based on the ORION-1 and ORION-3 trials, virtually all statin-intolerant patients taking Leqvio (inclisiran) experience some reduction in LDL-C, with approximately 0% showing no change in their LDL cholesterol levels. 1

Efficacy of Inclisiran in Statin-Intolerant Patients

Inclisiran (Leqvio) demonstrates remarkable consistency in producing LDL-C reductions across patient populations, including those with statin intolerance:

• In the ORION-1 trial, which included patients with documented statin intolerance, inclisiran produced dose-dependent LDL-C reductions of 30-45% 1
• The ORION-3 extension trial showed that these reductions were maintained at approximately 45% through 4 years of treatment 1
• Almost all patients treated with inclisiran maintained significant LDL-C reductions at 180 days post-treatment 1

Response Patterns in Statin-Intolerant Patients

While the evidence doesn't specifically quantify the exact percentage of non-responders among statin-intolerant patients taking Leqvio, the data suggests:

• The LDL-C reduction pattern in statin-intolerant patients appears similar to those on statin therapy 1
• Some variability in response exists, with 17-52% of patients returning to within 20% of their baseline LDL-C levels (not complete non-response) depending on dosing 1
• The standard dosing regimen (300mg at day 1, day 90, then every 6 months) consistently maintains approximately 45% LDL-C reduction in the vast majority of patients 1

Comparative Efficacy in Statin-Intolerant Population

Leqvio offers significant advantages for statin-intolerant patients compared to other non-statin therapies:

• Inclisiran provides approximately 45% LDL-C reduction, significantly better than ezetimibe (18-24%) or bempedoic acid (15-24% as monotherapy) 1, 2
• PCSK9 inhibitors as a class show consistent efficacy in statin-intolerant patients, with alirocumab demonstrating 54.8% LDL-C reduction compared to 20.1% with ezetimibe in this population 1
• Inclisiran's twice-yearly dosing schedule may improve adherence compared to other PCSK9 inhibitors requiring more frequent administration 2

Clinical Implications for Statin-Intolerant Patients

For patients with confirmed statin intolerance requiring LDL-C reduction:

• Inclisiran represents a highly effective option with virtually universal response 1
• The International Lipid Expert Panel (ILEP) recommends considering PCSK9 modulators like inclisiran when targets cannot be achieved with other therapies in statin-intolerant patients 1
• For patients at extremely high cardiovascular risk, combination therapy may be necessary to achieve target LDL-C levels <40 mg/dL (1 mmol/L) 1

Potential Pitfalls and Considerations

• Before concluding true statin intolerance, a systematic rechallenge process is recommended, as many patients labeled "statin intolerant" may tolerate a different statin or dosing regimen 2
• Single non-statin agents may not provide sufficient LDL-C lowering for high-risk patients; combination therapy may be necessary 2
• While inclisiran is highly effective, the ORION-3 trial population included only 23% with diabetes and 33% not taking statin therapy, so specific response rates in these subgroups may vary 1

In conclusion, the evidence strongly suggests that virtually all statin-intolerant patients experience meaningful LDL-C reduction with Leqvio, with no reported cases of complete non-response in the clinical trials that included this population.