Physicians' Academy for Cardiovascular Education

Phase 2 dose-finding study with PCSK9i in children and adolescents with HeFH

PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study

Literature - Daniels S, Caprio S, Chaudhari U et al., - J Clin Lipidol. 2020. doi: 10.1016/j.jacl.2020.03.001.

Introduction and methods

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder that is characterized by elevated LDL-c levels and increased risk of CV events [1-3]. It has been shown that early initiation of lipid lowering therapy is effective in reducing surrogate markers of CVD in youth [4]. The PCSK9 inhibitor alirocumab lowers LDL-c in adults, but is not approved in pediatric patients [5-7]. This open-label study evaluated the efficacy, safety and optimal dosing of alirocumab in a phase 2 trial (ODYSSEY KIDS) children and adolescents (8 to 17 years) with HeFH.

A total of 42 HeFH patients enrolled. Participants were 8 to 17 years old (mean age 12.4 years), had a body weight (BW) ≥25 kg, and LDL-c ≥130 mg/dL despite being on optimal statin or other lipid-modifying therapies (95% of patients were on a statin). Patients were enrolled into 4 cohorts with different dosing regimens: Cohort 1 (n=10): 30 mg (BW <50 kg) or 50 mg (BW ≥50 kg) alirocumab Q2W; cohort 2 (n=10): 40 mg (BW <50 kg) or 75 mg (BW ≥50 kg) Q2W; cohort 3 (n=11): 75 mg (BW <50 kg) or 150 mg (BW ≥50 kg) Q4W; cohort 4 (n=11): 150 mg (BW <50kg) or 300 mg (BW ≥50kg) Q4W.

After a screening period of up to 6 weeks, patients received treatment with alirocumab for 8 weeks (12 weeks in cohort 4), followed by a follow-up period of 6-8 weeks in cohorts 1-3. Cohort 4 had no follow-up period. Patients who successfully completed the main phase (open-label dose-finding period [OLDFI]), could enter the open-label extension (OLE) phase. After completion of the first 3 cohorts, the dosing regimen of cohort 2 was selected for the planned phase 3 study. Patients from cohorts 1 to 3 received the regimen of cohort 2 during the OLE period. Patients in cohort 4 remained on their initial regiment during the OLE period. Efficacy and Pharmacokinetics were analysed from baseline to week 8 (OLDFI period). Safety of the treatment was analyzed in combined OLDFI and OLE periods.

The primary endpoint was percentual change in LDL-c from baseline to week 8. Safety analysis was based on treatment emergent adverse events (TEAEs).

Main results


This phase 2 dose-finding study showed that PCSK9 inhibitor alirocumab decreased LDL-c levels and was generally well tolerated in pediatric HeFH patients. However, further investigation is required. The doses/dosing regimens used in cohorts 2 (40 mg [BW <50 kg] or 75 mg [BW ≥50 kg] Q2W) and 4 (150 mg [BW <50kg] or 300 mg [BW ≥50kg] Q4W) were selected for further evaluation in a subsequent phase 3 trial in children and adolescents with HeFH.


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