Table 1

Pipeline of drugs being evaluated in phase III clinical trials for SLE19

DrugMechanism of actionOverview of current phase IIIOverview of phase II/III development in SLE
AbataceptT-cell costimulation modulator (cytotoxic T lymphocyte-associated antigen 4–IgG1 fusion)Efficacy and safety of abatacept in lupus nephritis on a background of MMF and GCS. Trial is ongoing.In a 52-week phase II/III trial involving patients with lupus nephritis, there was no difference between treatment groups and placebo in time to confirmed complete response (primary endpoint), although biological activity was observed. Treatment was well tolerated.37
AnifrolumabFully human, IgG1 κ monoclonal antibody that binds to and neutralises receptors of all type I IFNsTwo currently ongoing trials are evaluating the efficacy and safety of anifrolumab either at one or two different dosing regimens for patients with moderate-to-severe SLE. A third trial evaluating the long-term safety and tolerability of anifrolumab for patients with moderate-to-severe SLE is recruiting patients who completed one of the above phase III trials.In a phase IIb trial for patients with moderate-to-severe SLE who did not have active and severe lupus nephritis or neuropsychiatric SLE, a significantly greater percentage of patients receiving anifrolumab 300 mg every 4 weeks achieved an SRI(4) response at week 24 with sustained reduction of GCS compared with placebo (primary endpoint).28
AtaciceptTACI-Fc fusion protein that binds BAFF and APRILTrial has been completed and results are published.30In a phase II/III trial, atacicept did not improve flare rate (primary endpoint) or time to first flare (main secondary endpoint) during a 52-week trial compared with placebo.30 However, a post hoc analysis indicated that patients with large baseline BAFF and APRIL concentrations may benefit more with this agent.31 More recently, results from a 24-week phase IIb trial showed no significant improvement in SRI(4) with atacicept treatment versus placebo (primary endpoint).32 However, patients with high disease activity did demonstrate significant improvements with atacicept versus placebo in SRI(6) response and incidence of flares.32
21-mer peptide derived from small nuclear riboprotein U1-70K, which is phosphorylated at Ser140Efficacy and safety of Lupuzor plus standard of care for patients with SLE
Trial is ongoing.
In a phase IIb trial, a significantly greater percentage of patients achieved SRI(4) response at week 12 with Lupuzor given once every 4 weeks compared with placebo (primary endpoint). Treatment was well tolerated in general.47
RituximabAnti-CD20 monoclonal antibody (B cell)Evaluation of rituximab plus MMF for flare reduction and steroid-sparing benefit for patients with lupus nephritis (RITUXILUP). Trial is ongoing.Although previous phase II/III trials did not meet their primary endpoint,43 44 additional clinical studies in combination with different drugs and under various conditions are being explored.
VoclosporinImmunosuppressant, calcineurin inhibitorEfficacy and safety of voclosporin in patients with active lupus nephritis. Trial is currently recruiting patients.In a completed phase IIb trial, at 48 weeks of treatment, 49% of patients with lupus nephritis achieved complete remission with the lower dosage voclosporin regimen (23.7 mg two times per week) compared with 24% in the control arm (P<0.001).48
  • APRIL, a proliferation-inducing ligand; BAFF, B-cell activating factor; GCS, glucocorticosteroid; IFN, interferon; MMF, mycophenolate mofetil; SRI(4), SLE Responder Index (SRI) with ≥4 point reductions; SRI(5), SRI with ≥5 point reductions; SRI(6), SRI with ≥6 point reductions TACI, transmembrane activator and CAML (calcium-modulating cyclophilin ligand) interactor.