Alirocumab was associated with consistent reductions in low-density lipoprotein cholesterol (LDL-C) and had similar safety results across body mass index (BMI) subgroups, according to a study published in Diabetes and Metabolism.
Researchers investigated whether baseline BMI had an effect on the efficacy and safety of alirocumab, a PCSK9 monoclonal antibody, using pooled data from 10 phase 3 ODYSSEY trials (n=4975) in which alirocumab was compared with placebo/ezetimibe. In 2 trials, alirocumab was delivered at 150 mg every 2 weeks, and in 8 trials it was delivered at 75 mg every 2 weeks with a possible increase to 150 mg after 12 weeks of treatment based on week 8 LDL-C level. The efficacy and safety of alirocumab were assessed in groups defined according to baseline BMI (≤25, >25 to 30, >30 to 35, and >35 kg/m2).
Participants in the higher BMI subgroups had lower baseline LDL-C levels. Participants receiving alirocumab had greater reductions in LDL-C levels from baseline to weeks 12 and 24 compared with those receiving placebo/ezetimibe (Pinteraction = .7119). These reductions were of comparable magnitude, regardless of BMI at baseline. Between 69.8% and 76.4% of patients receiving alirocumab and 9.7% to 18.4% receiving a control treatment achieved LDL-C levels <1.81 mmol/L (ie, <70 mg/dL) after 24 weeks similarly across BMI subgroups.
A greater percentage of patients in the higher vs lower BMI subgroups required an alirocumab dose increase: 22.5%, 24.9%, 31.7%, and 27.2% of patients with BMIs ≤25, >25 to 30, >30 to 35, and >35 kg/m2, respectively (P =.0343). Adverse events were comparable, regardless of BMI, and injection-site reaction frequency was higher in participants who received alirocumab (5.1%-8.2% across BMI categories) compared with a control treatment (3.6%-4.8%).
Limitations of the study include its post-hoc design, the limited duration of the trials for assessing long-term safety, and the fact that the analysis was performed on postrandomization subgroups.
“[T]his analysis provides clinically important evidence that, in the rapidly growing number of individuals with high body weight worldwide, the anti-PCSK9 antibody alirocumab provides consistent LDL-C reductions,” noted the investigators. “Importantly, the analysis reveals that alirocumab was well tolerated across all BMI subgroups, including both [patients with] very-low and very-high BMI, with no unexpected safety concerns.”
Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals Inc.
Tinahones FJ, Laufs U, Cariou B, et al. Alirocumab efficacy and safety by body mass index: A pooled analysis from 10 phase 3 ODYSSEY trials. Diabetes Metab. 2020;46(4):280-287.