Alirocumab efficacy and safety by body mass index: A pooled analysis from 10 Phase 3 ODYSSEY trials

• Published in: Diabetes & metabolism Vol. 46; no. 4; pp. 280 - 287
• Main Authors: Tinahones, F.J., Laufs, U., Cariou, B., Louie, M.J., Yang, J., Thompson, D., Leiter, L.A.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-09-2020
• Subjects: Alirocumab; Body mass index; LDL-C; Obesity; PCSK9 inhibitor; Body mass index; Obesity; PCSK9 inhibitor; Alirocumab; LDL-C
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2019.101120

Increased body mass index (BMI) contributes to cardiovascular risk and may influence efficacy of therapeutic antibodies. We investigated the effect of baseline BMI on efficacy and safety of alirocumab, a PCSK9 monoclonal antibody.
In a post-hoc analysis, data were pooled from 10 Phase 3 trials (n=4975) of alirocumab vs. placebo/ezetimibe controls. Alirocumab dose was 150mg every 2 weeks in two trials, and 75mg every 2 weeks with possible increase to 150mg at 12 weeks (based on Week 8 low-density lipoprotein cholesterol [LDL-C]) in eight trials. Efficacy/safety data were assessed in baseline BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2.
Baseline LDL-C levels were lower among patients in the higher BMI subgroups. Significant LDL-C reductions from baseline were observed at Weeks 12 and 24 for alirocumab vs. controls, of similar magnitude regardless of baseline BMI (interaction P-value=0.7119). LDL-C<1.81mmol/L (<70mg/dL) was achieved at Week 24 by 69.8–76.4% of alirocumab-treated patients and 9.7–18.4% of control-treated patients, with no pattern by BMI. A greater proportion of patients in higher vs. lower BMI subgroups required alirocumab dose increase (P=0.0343); proportions were 22.5%, 24.9%, 31.7%, and 27.2% of patients across BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2, respectively. Adverse event frequencies were similar regardless of BMI; injection-site reaction frequency was higher with alirocumab (5.1–8.2% across BMI categories) vs. controls (3.6–4.8%).
Alirocumab provided consistent LDL-C reductions, with similar safety findings across BMI subgroups.