Safety and efficacy of alirocumab 150 mg every 2 weeks, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody: A Phase II pooled analysis

Abstract

Background. Alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is in Phase III development for the treatment of hypercholesterolemia. In Phase II studies, 150 mg every 2 weeks (Q2W) was the highest Q2W dose studied, and it is currently the highest Q2W dose under development. To better assess the safety and efficacy of this dose, data across three Phase II studies were pooled. Methods. We analyzed data from three double-blind, randomized, placebo-controlled Phase II studies of 8 or 12 weeks’ duration. In the current analysis, 77 patients were randomized to the control group and 108 were randomized to alirocumab 150 mg Q2W administered via a single 1 mL subcutaneous injection. Results. Adverse events (AEs) occurred in 58.3% of alirocumab patients compared with 54.5% of placebo-controlled patients. The most common AE was mild, transient injection-site reactions. No signal for muscle symptoms such as myalgia and no cases of neurocognitive effects were reported or observed. One alirocumab patient, also receiving atorvastatin 80 mg/day, had an increase in aspartate transaminase 3 to 5 times the upper limit of normal. Alirocumab 150 mg Q2W reduced low-density lipoprotein cholesterol (LDL-C) from baseline by 68.4% compared with 10.5% for the control group. More than 90% of patients achieved an LDL-C target of < 70 mg/dL with alirocumab versus 8% with control. Marked reductions in other atherogenic lipids and modest increases in high-density lipoprotein cholesterol were also observed. Conclusion. At the highest Q2W dose under development (150 mg), alirocumab appears well tolerated and produces robust LDL-C reductions. These data suggest that alirocumab 150 mg Q2W is an appropriate dose for further evaluation in Phase III trials.

Keywords :

• Alirocumab
• hypercholesterolemia
• low-density lipoprotein cholesterol
• proprotein convertase subtilisin/kexin type 9

Acknowledgments

The first author wrote the first draft of the manuscript. All authors had full access to the data and vouch for the accuracy and completeness of the analysis. Statistical analyses were performed by employees of the sponsor. Prime Medica, an independent consulting group compensated by the sponsor, provided editorial assistance and logistical support. Sanofi and Regeneron funded this analysis. Betty Thompson and Rob Campbell of Prime Medica (an independent firm supported by Sanofi and Regeneron) provided medical writing support.

Declaration of interest

M. J. Koren is employed by a company that has received research funds and consulting fees from Regeneron and Sanofi. E. M. Roth and J. M. McKenney also work for a company that has received research funding from Regeneron and/or Sanofi. E. M. Roth has also been a speaker for AstraZeneca and Merck, and has acted as a consultant for Regeneron/Sanofi. D. Gipe and R. Wu are employees of Regeneron. C. Hanotin and A–C. Ferrand are employees of Sanofi. R. Dufour has received consultancy fees from Sanofi, research funding from Sanofi, Regeneron, Amgen, Pfizer, Acasti, and Novartis and been a speaker and/or advisor for Regeneron, Sanofi and Amgen.

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