Furie R. BLISS-LN: A randomized, double-blind, placebo-controlled Phase 3 trial of intravenous belimumab in patients with active lupus nephritis. Presented at EULAR 2020 Congress; June 3-6 (virtual meeting).
Furie reports research support and consulting fees from GlaxoSmithKline.
Data from the largest lupus nephritis study to date suggested that belimumab plus standard therapy “significantly improves” renal response compared with standard therapy alone, according to data presented at the EULAR 2020 Congress.
“The impetus to evaluate belimumab in lupus nephritis was based on the successful outcomes of the two phase 3 studies, BLISS-52 and BLISS-76,” Richard Furie, MD, of Northwell Health, in Great Neck, New York, told attendees in a webcast. “The post hoc analysis of the phase 3 studies demonstrated improvements in renal parameters of the patients who had renal involvement at baseline. Finally, there is evidence for increased serum BAFF levels in lupus nephritis, along with findings of heightened intra-renal BAFF production in patients with nephritis.”
“Neutralizing BAFF and down-regulating auto-reactive B-cell function in kidneys represents a compelling therapeutic approach to lupus nephritis,” he added. “Belimumab, a recombinant human IgG1 lambda monoclonal antibody that inhibits BAFF, is approved for the treatment of active auto-antibody-positive SLE.”
To examine the efficacy and safety of intravenous belimumab plus standard therapy, compared with a placebo, among patients with active lupus nephritis, Furie and colleagues conducted the phase 3 BLISS-LN study, a randomized, double-blind, 104-week trial. Investigators randomly assigned 448 adults with SLE and biopsy-confirmed lupus nephritis were to receive either 10 mg/kg of belimumab or a placebo alongside standard therapy. The efficacy analysis included 223 participants in each group, while the safety analysis featured 224 in each group.
The primary endpoint was Primary Efficacy Renal Response (PERR), defined as a urine protein creatinine ratio of 0.7 or less, estimated glomerular filtration rate within 20% of the pre-flare value, or 60 mL/min/1.73m2 or greater, and no rescue therapy at week 104. Key secondary endpoints were complete Renal Response at week 104, PERR at week 52, time to renal-related event or death. Other endpoints included time to PERR or complete renal response sustained through week 104, a SLEDAI-S2K score less than 4 at week 104 and safety.
According to Furie, 43% of patients who received belimumab alongside standard therapy achieved PERR at week 104, compared with 32.3% of those in the placebo group (OR = 1.55; 95% CI, 1.04-2.32). Further, more patients in the belimumab achieved key secondary and other efficacy endpoints than those who received a placebo.
Regarding safety, 95.5% of patients in the belimumab, and 94.2% of those in the placebo group, demonstrated one or more adverse event, with 25.9% and 29.9% patients, respectively, developing one or more serious adverse event. The discontinuation rate due to adverse events was 12.9% in both groups, with fatal adverse-event rates of 1.8% in the belimumab group and 1.3% in the placebo group.
“In the largest lupus nephritis study to date, data from BLISS-LN demonstrate that belimumab plus standard therapy significantly improved multiple lupus nephritis renal responses versus standard therapy alone,” Furie said. “In addition, belimumab plus standard therapy maintained an acceptable safety profile.”