The discovery and development of belimumab: the anti-BLyS-lupus connection

Nat Biotechnol. 2012 Jan 9;30(1):69-77. doi: 10.1038/nbt.2076.


For the first time in more than 50 years, the US Food and Drug Administration has approved a drug specifically for the treatment of systemic lupus erythematosus (SLE). This drug, belimumab (Benlysta), is a human monoclonal antibody that neutralizes the B-cell survival factor, B-lymphocyte stimulator (BLyS). The approval of belimumab combined a pioneering approach to genomics-based gene discovery, an astute appreciation of translational medicine, a disciplined clinical strategy, a willingness to take calculated risks, a devoted cadre of patients and physicians and a healthy dose of serendipity. Collectively, these efforts have provided a model for the development of a new generation of drugs to treat the broad manifestations of SLE. However, as a substantial percentage of SLE patients do not respond to belimumab, further research is needed to better characterize the pathogenetic mechanisms of SLE, identify additional therapeutic targets, and develop effective and nontoxic novel agents against these targets.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • B-Cell Activating Factor / antagonists & inhibitors
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Controlled Clinical Trials as Topic
  • Drug Approval*
  • Drug Resistance / genetics
  • Humans
  • Lupus Erythematosus, Systemic / drug therapy*
  • Mice
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • B-Cell Activating Factor
  • TNFSF13B protein, human
  • belimumab