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

Authors Lenert A, Niewold TB, Lenert P

Received 12 December 2016

Accepted for publication 10 February 2017

Published 13 March 2017 Volume 2017:11 Pages 747—757

DOI https://doi.org/10.2147/DDDT.S114552

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rasika Samarasinghe

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Frank Boeckler

Aleksander Lenert,1 Timothy B Niewold,2 Petar Lenert3

1Division of Rheumatology, University of Kentucky, Kentucky Clinic, Lexington, KY, 2Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN, 3Division of Immunology, Department of Internal Medicine, The University of Iowa, Iowa City, IA, USA

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.

Keywords:
BAFF, APRIL, lupus, B cells, blisibimod

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