LERODALCIBEP-LIGA INJ,SOLN

Clinical Criteria Summary

End-stage renal disease on dialysis
Advanced heart failure with limited prognosis
Severe comorbid non-cardiovascular condition that is expected to limit life expectancy
Pregnant or lactating status

History of atherosclerotic cardiovascular disease (ASCVD)
Severe hypercholesterolemia without ASCVD (e.g., heterozygous familial hypercholesterolemia [HeFH], low density lipoprotein cholesterol [LDL-C] > 190 mg/dL)

Contraindication, intolerance to, or insufficient LDL-C reduction requiring further LDL-C lowering to reduce ASCVD risk consistent with established guidelines after a trial of:
Maximally tolerated dose of statin (may be none; confirmed statin intolerance defined as intolerance to at least 2 statins, one at the lowest approved daily dose, and trial of alternate day dosing)
Ezetimibe
Monoclonal antibody inhibitor of PCSK9 (mAb PCSK9i, e.g., alirocumab or evolocumab)
Inclisiran
Combination therapy with mAb PCSK9i, inclisiran, or lerodalcibep is not supported by evidence and should not be performed; inadequate LDL-C reduction warrants agent replacement rather than combination
Use of a mAb PCSK9i with proven cardiovascular benefit (e.g., alirocumab or evolocumab) may be utilized in patients with elevated lipoprotein a who have not met LDL-C goals with maximally tolerated dose of statin, without requiring ezetimibe

Females who are pregnant or plan to become pregnant: Lerodalcibep should not be started or should be discontinued when pregnancy is recognized; treatment for hypercholesterolemia is generally not needed during pregnancy
Females who are lactating/breastfeeding or planning to do so: Decision based on consideration of risks and benefits regarding the mother’s need and potential side effects on the infant, given lack of data on the effect of lerodalcibep on milk production or the infant

Adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including HeFH
Effect on CV events has not been established; no clinical outcome trial design or details published

Patients with CVD or at high risk for CVD (LDL-C >70 mg/dL if CVD present; LDL-C >100 mg/dL and TG <400 mg/dL if high risk without CVD)
Patients with HeFH
Patients with or at high/very high risk for ASCVD who do not reach LDL-C goals on maximally tolerated statins plus other oral LDL-C lowering agents
Secondary prevention for patients at very high risk, including those with HeFH receiving maximally tolerated statins plus ezetimibe requiring additional LDL-C reduction to achieve goals

Must be receiving maximally tolerated statins plus other lipid therapies (or ezetimibe)
Requires additional LDL-C reduction to achieve LDL-C goals
Unable to tolerate alirocumab, evolocumab, or inclisiran

No boxed warnings or contraindications
Risk of injection site reactions (ISR) and other adverse events including nasopharyngitis, diarrhea, nausea, and peripheral edema
Discontinue when pregnancy is recognized; evidence for use in pregnant women is insufficient
Lactation: Lack of evidence; consider developmental/health benefits of breastfeeding alongside mother’s clinical need and potential effects on the breastfed infant