Table 1.
Pivotal trials of biologic therapies in systemic lupus erythematosus (SLE).
| Therapeutic target | Drug under investigation | Pivotal clinical trials | Current status |
|---|---|---|---|
| Chimeric anti-CD20 monoclonal antibody | Rituximab | Failed to meet primary endpoints in LUNAR (nephritis) and EXPLORER (non-nephritis) phase III studies. | Phase III trial of rituximab and mycophenolate mofetil with corticosteroid minimizing regimen ongoing |
| Humanized anti-CD22 monoclonal antibody (nondepleting) | Epratuzumab | Safe and well tolerated ALLEVIATE study EMBLEM studies | Phase III study ongoing |
| Humanized anti-CD20 monoclonal antibody | Ocrelizumab | BELONG study terminated due to a high incidence of opportunistic infections | No studies ongoing |
| TACI-Ig fusion protein | Atacicept | Phase II study terminated due to risk of serious infections | Phase II trial (ADDRESS II) ongoing |
| Humanized anti-BLyS monoclonal antibody | Belimumab | BLISS-52 and BLISS-76 showed efficacy excluding severe renal and neuropsychiatric disease | Phase III trial in lupus nephritis ongoing trial of belimumab following rituximab induction therapy planned |
| Humanized anti-BAFF monoclonal antibody | Blisibimod | Safe and well tolerated in early phase trials | Phase III study ongoing |
| Humanized anti-BAFF monoclonal antibody | Tabalumab | ILLUMINATE 1: failed to meet primary endpoint ILLUMINATE 2: effective at higher study dose | To be determined |
| CTL4-Ig fusion protein | Abatacept | Failed phase II trial in nonrenal lupus. Phase III trial in lupus nephritis failed. Subgroup analysis using different outcome measures showed positive results however. | Further phase III trial pending |
| Humanized anti-IL6 monoclonal antibody | Tocilizumab | Well tolerated in phase I trial | To be determined |
| Humanized anti-IL6 monoclonal antibody | Sirukumab | Not efficacious in reducing proteinuria, increased risk of infection | No studies ongoing |
| Humanized anti-IFNα monoclonal antibody | Rontalizumab | Failed phase II study | No studies ongoing |
| Humanized anti-IFNα monoclonal antibody | Sifalimumab | Well tolerated and efficacious in phase 2b trial | To be determined |
| Humanized anti-IFNα receptor 1 monoclonal antibody | Anifrolumab | Significant impact on interferon gene signature | Phase III trial planned |
BAFF, B-cell activating factor; BLyS, B lymphocyte stimulator; CTL4-Ig,cytotoxic T lymphocyte antigen-4 immunoglobulin; IFNα, interferon α; IL6, interleukin 6; TACI-Ig, transmembrane activator and calcium modulator and cyclophilin ligand interactor immunoglobulin.