| Target |
Agent |
Mechanism of Action |
Key Clinical Trials (*denotes ongoing or upcoming trial) |
Primary Endpoint Met |
| B cells |
Rituximab |
Chimeric monoclonal anti-CD20 antibody |
Phase III (EXPLORER) [67]: SLE
Phase III (LUNAR) [68]: lupus nephritis
Phase III (RING) [69]*: lupus nephritis |
No
No
|
| B cells |
Belimumab |
BLyS inhibitor |
Phase III (BLISS 52) [70]: SLE
Phase III (BLISS 76) [71]: SLE
Phase III (BLISS-LN) [73]*: lupus nephritis
Phase III/IV (EMBRACE) [75]*: SLE in African Americans |
Yes
Yes (only for 10 mg/kg Belimumab group) |
| B cells |
Atacicept |
BLyS and APRIL inhibitor |
Phase II/III (APRIL-LN) [79]: lupus nephritis
Phase II/III [80] (APRIL SLE)*: SLE |
No (study prematurely terminated) |
| B cells |
Abetimus |
B cell tolerogenic DNA-oligomeric construct active against anti-dsDNA |
Phase II/III [82]: lupus nephritis
Phase III [83]: lupus nephritis |
No
No |
| B cells |
Ocrelizumab |
Humanized monoclonal anti-CD20 antibody |
Phase III (BEGIN) [84]: SLE
Phase III (BELONG) [85]*: lupus nephritis |
No (study prematurely terminated) |
| B cells |
Epratuzumab |
Humanized monoclonal anti-CD22 antibody |
Phase II (EMBLEM) [87]: SLE
Phase III (EMBODY 1) [88]*: SLE |
Yes |
| T cells |
Abatacept |
T-cell costimulation blockade |
Phase IIb [89]: SLE
Phase II/III [90]: lupus nephritis
Phase II (ACCESS), Phase III [91,92]*: lupus nephritis |
No
No (study prematurely terminated) |
| T cells |
Rapamycin |
Regulation of mitochondrial transmembrane potential and calcium flow |
Phase I [93]: SLE
Phase II [94]*: SLE |
Preliminary efficacy observed |
| T cells |
N-acetylcysteine |
mTOR inhibitor in T lymphocytes |
Phase I/II [95]: SLE |
Preliminary efficacy observed (except for 1.2 g daily N-acetylcysteine group) |
| T cells |
R788 |
Spleen tyrosine kinase inhibitor |
None (only murine lupus data) [96,97] |
|
| T cells |
BG9588 |
Humanized anti-CD40 ligand antibody |
Phase II [99]: SLE |
No (study prematurely terminated) |
| T cells |
Laquinimod |
Promotes TH2 over TH1 response |
Phase IIa [101]*: SLE
Phase IIa [102]*: lupus nephritis |
|
| T cells |
Paquinimod |
Promotes TH2 over TH1 response |
Phase Ib [103]: SLE |
N/A |
| Cytokines |
Sifalimumab |
IFN-alpha inhibitor |
Phase I [104]: SLE
Phase II, Phase IIb [105,106]*: SLE |
Preliminary efficacy observed |
| Cytokines |
Rontalizumab |
IFN-alpha inhibitor |
Phase I [107]: SLE
Phase II (ROSE) [108]: SLE |
N/A
No |
| Cytokines |
Tocilizumab |
Humanized monoclonal antibody against IL-6 receptor |
Phase I [114]: SLE |
Preliminary efficacy observed |
| Cytokines |
B-N10 |
Murine anti-IL-10 monoclonal antibody |
Phase I [115]: SLE |
Preliminary efficacy observed |
| Cytokines |
Infliximab |
Chimeric TNF-alpha inhibitor |
Phase I (two trials) [116,117]: SLE
Phase II/III (TRIAL) [121]: SLE |
Preliminary efficacy observed
No (study prematurely terminated) |
| Cytokines |
Etanercept |
Soluble TNF-receptor fusion protein |
Phase II [122]: SLE |
No (study prematurely terminated) |
