Spotlight on blisibimod and its potential in the treatment of systemic lupus erythematosus: Evidence to date

Aleksander Lenert, Timothy B. Niewold, Petar Lenert

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF. Furthermore, blisibimod has a unique structure built on four high-affinity BAFF-binding peptides fused to the IgG1-Fc carrier. It was tested in phase I and II trials in SLE where it showed safety and tolerability. While it failed to reach the primary endpoint in a recent phase II trial, post hoc analysis demonstrated its efficacy in SLE patients with higher disease activity. Based on these results, blisibimod is currently undergoing phase III trials targeting this responder subpopulation of SLE patients. The advantage of blisibimod, compared to its competitors, lies in its higher avidity for BAFF, but a possible drawback may come from its immunogenic potential and the anticipated loss of efficacy over time.

Original languageEnglish (US)
Pages (from-to)747-757
Number of pages11
JournalDrug Design, Development and Therapy
Volume11
DOIs
StatePublished - Mar 13 2017

Fingerprint

AMG623 peptibody
Systemic Lupus Erythematosus
B-Cell Activating Factor
Therapeutics
Safety
Biological Factors
B-Lymphocytes
Tumor Necrosis Factor-alpha
Immunoglobulin G
Monoclonal Antibodies
Clinical Trials
Peptides
Membranes

Keywords

  • APRIL
  • B cells
  • BAFF
  • Blisibimod
  • Lupus

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Spotlight on blisibimod and its potential in the treatment of systemic lupus erythematosus : Evidence to date. / Lenert, Aleksander; Niewold, Timothy B.; Lenert, Petar.

In: Drug Design, Development and Therapy, Vol. 11, 13.03.2017, p. 747-757.

Research output: Contribution to journalReview article

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