TY - JOUR
T1 - Spotlight on blisibimod and its potential in the treatment of systemic lupus erythematosus
T2 - Evidence to date
AU - Lenert, Aleksander
AU - Niewold, Timothy B.
AU - Lenert, Petar
N1 - Publisher Copyright:
© 2017 Lenert et al.
PY - 2017/3/13
Y1 - 2017/3/13
N2 - 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.
AB - 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.
KW - APRIL
KW - B cells
KW - BAFF
KW - Blisibimod
KW - Lupus
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U2 - 10.2147/DDDT.S114552
DO - 10.2147/DDDT.S114552
M3 - Review article
C2 - 28331294
AN - SCOPUS:85015300545
SN - 1177-8881
VL - 11
SP - 747
EP - 757
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -