Progress of biologics/targeted therapy in SLE Save

We are in a transformative era in SLE which generates excitement to both physicians and people living with lupus. We now have four licensed biologics/targeted therapies (i.e. belimumab, voclosporin and obinutuzumab for active lupus nephritis, and belimumab and anifrolumab for active non-renal SLE). Moreover, many other agents with different mode of action and administration are in late phase trials. In this article, we will preview some data that will be presented at this year’s EULAR 2026 Congress in London, United Kingdom.

Obinutuzumab was the first B-cell depleting therapy that met its primary endpoint in a phase III randomised controlled trial (RCT) for the treatment of active lupus nephritis (REGENCY), and subsequently led to its approval by US FDA in October 2025 and by EMA in December 2025. The efficacy and safety data of obinutuzumab in a phase III RCT of active non-renal SLE (ALLEGORY) were recently published in New England Journal of Medicine in March 2026 DOI: 10.1056/NEJMoa2516150. Obinutuzumab + standard therapy met their primary endpoint, SRI-4 and 5 other key secondary endpoints over placebo + standard therapy. At this year’s EULAR congress, Prof Furie will present the efficacy of obinutuzumab in relation to other clinically meaningful endpoints, DORIS remission and Lupus Low Disease Activity State (POS0683), as well as data on pharmacodynamic effects of obinutuzumab in terms of the depth of B-cell depletion, reduction in autoantibodies and normalisation of complement level (POS0310). 

What are other new promising therapies in SLE? Prof Morand (OP0337) will present tolerability and safety data from a long-term extension study of a Phase 2 RCT of enpatoran, a first-in-class oral small molecule toll-like receptor 7/8 inhibitor. In this RCT evaluating two cohorts, A [CLASI-A ≥8 at screening and BL] and B [at least moderate activity as defined by BILAG-2004], participants receiving enpatoran who completed the first 24 weeks continued the same drug allocation up to 48 weeks, while those on placebo switched to enpatoran 100mg BID. Data pertaining to the efficacy of enpatoran at 48 weeks in participants with CLASI-A ≥8 at screening and BL will also be presented. 

Following the success of nipocalimab, an anti-neonatal Fc receptor (FcRn) monoclonal antibody that reduces circulating IgG, including pathogenic IgG autoantibodies in a phase II RCT in Sjogren’s disease, Prof Furie (LB0007) will present the efficacy and safety of a phase 2 RCT of nipocalimab in patients with autoantibodies positive SLE, with moderate to severe disease activity as defined by SLEDAI-2K and BILAG-2004, as well as having active skin disease (CLASI≥6) and/or active arthritis (≥4 active joints). The investigators will also present the primary endpoint (SRI-4) and a key secondary endpoint (LLDAS) at Week 52 based on 3 predefined biomarker-based populations: autoantibody-positive, autoantibody-high, and interferon [IFN]-high. 

Although many Bruton’s tyrosine kinase inhibitors have been licensed for the treatment of B-cell haematological malignancies, their extrapolation to SLE has been somewhat disappointing. Many agents when used as monotherapy have failed in SLE trials. However, there may be a light at the end of the tunnel. Dr Li (POS0713) will present efficacy and safety of orelabrutinib, a novel oral, highly-selective, irreversible inhibitor of BTK in a phase 2 RCT of moderate to severely active SLE (i.e. SLEDAI-2K ≥8) in China. It will be interesting to see how the treatment will fare in a phase III RCT and if it will be investigated globally for the findings to be generalised.

Finally, beyond the usual conventional immunosuppressants (i.e. methotrexate, mycophenolate, azathioprine, tacrolimus, ciclosporin and leflunomide), data from an RCT in China will be presented by Dr Peng (LB0006). The investigators evaluated the efficacy and safety of oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor as add-on therapy in patients with active SLE who had an inadequate response to standard-of-care treatments.