Gevokizumab in type 1 diabetes mellitus: extreme remedies for extreme diseases?

Expert Opin Investig Drugs. 2014 Sep;23(9):1277-84. doi: 10.1517/13543784.2014.947026. Epub 2014 Jul 31.

Abstract

Introduction: Insulin is the cornerstone of type 1 diabetes mellitus (T1DM) therapy. However, it cannot achieve a delay in the onset or evolution of this condition, while cardiovascular morbidity remains an unquestionable threat.

Areas covered: In this review, the authors discuss gevokizumab (XOMA 052), a recombinant monoclonal antibody that can neutralize human IL-1β by binding to it. This is relevant, because this IL has been associated with β-cell toxicity in both diabetes types. Moreover, gevokizumab presents two major advantages: it spares IL-1α and it exhibits favorable pharmacokinetic properties. Gevokizumab has already proven its safety and efficacy in improving glycemic control, β cell function and inflammation markers in clinical trials in diabetic patients.

Expert opinion: Despite the very promising characteristics of gevokizumab, important questions remain to be answered. One important question is what to expect from a combination of this agent with insulin and if there is a subset of patients that might respond more favorably to treatment. We also need to know at what stage in the natural history of T1DM could gevokizumab be most efficacious, as well as its potential effects on cardiovascular outcomes.

Keywords: IL-1β; gevokizumab; inflammation; type 1 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use
  • Insulin-Secreting Cells / metabolism
  • Interleukin-1beta / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Interleukin-1beta
  • gevokizumab