Inclisiran Treatment Duration
Inclisiran can be administered indefinitely as a long-term treatment with a twice-yearly maintenance dosing regimen after initial doses at day 1 and day 90. 1, 2
Dosing Schedule and Administration
- The recommended dosage of inclisiran (Leqvio) is 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then every 6 months thereafter 1
- Inclisiran is administered as a subcutaneous injection in the abdomen, thigh, or upper arm 3
- The maintenance dosing schedule of twice yearly (every 6 months) is designed for long-term therapy and improved adherence 4
Duration of Effect and Efficacy
- In clinical trials, inclisiran demonstrated a mean placebo-corrected reduction in LDL-C of 50.7% at day 510, with a time-adjusted mean reduction of 50.5% 1, 2
- The effect of inclisiran on LDL-C is durable, with reductions maintained for up to 4 years in extension studies 5
- Following a single dose, LDL-C reduction is apparent within 14 days and mean reductions of 38% to 51% are observed 30 to 180 days post-dose 3
- At Day 180 after a single dose, LDL-C levels remain reduced by approximately 53% 3
Long-term Safety Profile
- Safety data from clinical trials supports the long-term use of inclisiran with a favorable safety profile similar to placebo 1, 6
- The most common adverse effects are injection site reactions (5.0% vs 0.7% for placebo), which are predominantly mild and not persistent 1
- No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger adult patients 3
- Extension studies have shown that inclisiran remains well-tolerated even with long-term use over multiple years 5
Special Populations and Considerations
- No dose adjustments are necessary for patients with mild, moderate, or severe renal impairment 3
- No dose adjustment is necessary in patients with mild to moderate hepatic impairment 3
- Inclisiran has not been studied in patients with end-stage renal disease or severe hepatic impairment 3
- The safety and effectiveness of inclisiran have not been established in pediatric patients 3
Ongoing Cardiovascular Outcomes Trials
- Two cardiovascular outcomes trials, ORION-4 and VICTORION-2P, are currently in progress to determine the effect of inclisiran on cardiovascular morbidity and mortality 1
- ORION-4 is following approximately 15,000 participants for a planned median duration of about 5 years 1
- Results from these long-term trials will provide additional data on the safety and efficacy of inclisiran over extended periods 7
Clinical Implications
- The twice-yearly maintenance dosing regimen of inclisiran offers a significant advantage for long-term adherence compared to other non-statin lipid-lowering therapies 6, 4
- Inclisiran can be used as a long-term therapy for patients who require additional LDL-C lowering despite maximally tolerated statin therapy 2
- The drug remains in circulation for less than 48 hours, but its effect lasts for over six months, supporting its long-term use with infrequent dosing 4