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Objective: Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE). Methods: During screening, patients with active, non–organ‐threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed). Patients with improved disease activity were randomized 1:1 to obexelimab 5 mg/kg intravenously or placebo once every 2 weeks until week 32 or loss of improvement (LOI). Results: In this study, 104 patients were randomized. Analysis of the primary endpoint, proportion of patients reaching week 32 without LOI, used an efficacy‐evaluable (EE) population defined as patients who completed the study or withdrew for flare or treatment‐related toxicity. This endpoint did not reach statistical significance: 21 of 50 obexelimab‐treated patients (42.0%) versus 12 of 42 patients (28.6%) treated with a placebo (P = 0.183). Time to LOI was increased in obexelimab‐treated patients versus patients treated with a placebo in the EE (hazard ratio [HR] 0.53, P = 0.025) and intention‐to‐treat (HR 0.59, P = 0.062) populations. In obexelimab‐treated patients, B cells decreased approximately 50%, and trough concentration and inclusion in baseline gene expression clusters with high B cell pathway modules were associated with increased time to LOI. Obexelimab was associated with infusion reactions but was generally safe and well‐tolerated. Conclusion: Although the primary endpoint was not reached, secondary analysis showed time to LOI was significantly increased in obexelimab‐treated patients, and analysis of patient subsets defined by gene expression patterns at baseline suggests a responding subpopulation. [ABSTRACT FROM AUTHOR]

Non‐White people are more likely to develop systemic lupus erythematosus (SLE) yet are underrepresented in SLE clinical trials. The efficacy and safety of drugs may be influenced by ancestry, and ancestrally diverse study populations are necessary to optimize treatments across the full spectrum of patients. However, barriers to entry into clinical trials are amplified in non‐White populations. To address these issues, a conference was held in Bethesda, Maryland, from October 15–16, 2019, entitled "Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies: Overcoming the Barriers." Conference participants included people with lupus, lupus physicians, lupus clinical trialists, treatment developers from biotechnology, social scientists, patient advocacy groups, and US government representatives (The Office of Minority Health, Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration). For all these groups, the organizers of the conference purposefully included people of non‐White ancestry. Decreased participation of non‐White SLE patients in clinical research was evaluated through historical, societal, experiential, and pragmatic perspectives, and several interventional programs to increase non‐White patient participation in SLE and non‐SLE research were described and discussed. The presentations and discussions highlighted the need for changes at the societal, institutional, research team, referring physician, and patient education levels to achieve equitable ancestral representation in SLE clinical studies. [ABSTRACT FROM AUTHOR]

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self‐identified Black race. Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.gov identifier: NCT01632241) was a 52‐week multicenter, double‐blind, placebo‐controlled trial in adults of self‐identified Black race with active SLE who received monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26‐week open‐label extension phase included patients who completed the double‐blind phase. The primary end point of the study was SLE Responder Index (SRI) response rate at week 52 with modified proteinuria scoring adapted from the SLE Disease Activity Index 2000 (SLEDAI‐2K) (SRI–SLEDAI‐2K). Key secondary end points included SRI response rate at week 52, time to first severe SLE flare, and reductions in prednisone dose. Results: The modified intent‐to‐treat population comprised 448 patients, of whom 96.9% were women and the mean ± SD age was 38.8 ± 11.42 years. The primary end point (improvement in the SRI–SLEDAI‐2K response rate at week 52) was not achieved (belimumab 48.7%, placebo 41.6%; odds ratio 1.40 [95% confidence interval 0.93, 2.11], P = 0.1068); however, numerical improvements favoring belimumab were observed, in which the SRI–SLEDAI‐2K response rates were higher in those who received belimumab compared with those who received placebo, especially in patients with SLE who had high disease activity or renal manifestations at baseline. The safety profile of belimumab was generally consistent with that observed in previous SLE trials. Adverse events were the primary reasons for double‐blind phase withdrawals (belimumab 5.4%, placebo 6.7%). Conclusion: The primary end point of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry. [ABSTRACT FROM AUTHOR]