A Pivotal Phase III, Randomized, Placebo-Controlled Study of Belimumab in Patients with Systemic Lupus Erythematosus Located in China, Japan, and South Korea

Abstract

Background/Purpose: SLE is an autoimmune disease associated with elevated levels of B Lymphocyte Stimulator (BLyS). This study assessed the efficacy and safety of belimumab (BLyS-specific inhibitor) 10mg/kg when added to standard of care therapy compared with placebo over 52 weeks (wks) in patients with SLE located in NE Asia (China, Japan, and S. Korea).

Methods: 707 patients with SLE age ≥18 yrs with a Safety of Estrogen in Lupus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI; SS) disease activity score of ≥8 at screening were randomized (2:1) 10mg/kg belimumab or placebo (NCT01345253, study BEL113750). Patients were dosed on Days 0, 14, 28 and then every 28 days through Wk 48, with a final evaluation at Wk 52. The primary endpoint was the SLE responder index (SRI) response rate at Wk 52 (reduction ≥4 points in SS score; no worsening (<0.3 increase) in Physician’s Global Assessment (PGA); no new British Isles Lupus Assessment Group (BILAG). A domain score or 2 new BILAG B domain scores vs baseline. Secondary endpoints included percent of patients with ≥4 point reduction in SS score over baseline at Wk 52, SRI7 responders (SRI and ≥7 points reduction in SS) at Wk 52, number of days of daily prednisone dose ≤7.5mg and/or reduced by 50% over 52 wks, and time to first severe modified SLE Flare Index (SFI) flare.

Results: The primary endpoint was reached as an SRI response at Wk 52 was achieved in 242/446 (54.3%) evaluable patients receiving belimumab vs 87/217 (40.1%) of placebo patients [odds ratio 2.03 (95% CI 1.43, 2.88), p<0.0001]. Benefits of belimumab therapy were also observed for all 4 secondary endpoints. 55.7% of patients receiving belimumab achieved a ≥4 point reduction in SS at Wk 52 vs 42.2% on placebo (odds ratio 2.00 (95% CI: 1.41, 2.83), [p=0.0001]). An SRI7 response rate of 32.7% was achieved on belimumab vs 23.5% for placebo (odds ratio 1.78 (95% CI: 1.15, 2.77) [p=0.0099]). Among 536 patients receiving >7.5 mg/day prednisone at baseline, the median number of days prednisone was reduced to ≤7.5 mg/day and/or by 50% from baseline over 52 wks was zero for both treatments, and the 75% percentile was larger for belimumab; 213.5 days vs 172 days, rank ANCOVA p=0.0288. Belimumab patients had a 50% lower risk of experiencing a severe SFI flare relative to placebo patients (hazard ratio=0.50, 95% CI: 0.34, 0.73), p=0.0004. The overall incidence of AEs was similar between placebo (75.7%) and belimumab (74.9%). The incidence of SAEs was higher for placebo (18.3%) vs belimumab (12.3%). There were similar rates of infectious SAEs in placebo patients (5.5%) and in belimumab patients (5.3%). There was one fatality reported in the placebo group and none in the belimumab group.

Conclusion: This is the fourth pivotal belimumab trial in SLE which has achieved statistical significance for the primary endpoint. All 4 pre-specified secondary endpoints also reached statistical significance. The safety profile of IV belimumab in this NE Asia population is consistent with belimumab IV and subcutaneous data to date; no new safety issues are identified. Disclosures: Study funded by GSK. Submission support provided by Louisa Pettinger, Fishawack Indicia Ltd, funded by GSK.