EVALUATING SIBEPRENLIMAB IN PATIENTS WITH IgA NEPHROPATHY: RESULTS FROM AN INTERIM ANALYSIS OF THE CHINA COHORT OF THE PHASE 3 VISIONARY TRIAL

Immunoglobulin A nephropathy (IgAN) accounts for 30%-53% of primary glomerular diseases in China. Up to 24% of Chinese patients with IgAN develop end-stage kidney disease within 6 years. Sibeprenlimab, a humanized IgG2 monoclonal antibody, selectively binds to and blocks the biological actions of a proliferation-inducing ligand (APRIL), a cytokine that plays a key role in the immune-mediated pathogenesis of IgAN. The safety and efficacy of sibeprenlimab are being evaluated in the ongoing VISIONARY trial (NCT05248646) in a global cohort of adults with IgAN. In a prespecified interim analysis (IA), sibeprenlimab met the primary endpoint, showing a 51.2% (P<0.0001) placebo (PBO)-adjusted reduction in 24-hour urinary protein to creatinine ratio (uPCR-24h) at 9 months. Here we report the IA results for the China cohort, assessing consistency with those from the global main cohort.

VISIONARY, a phase 3 double-blind, PBO-controlled trial in adults with biopsy-confirmed IgAN, is being conducted at 240 sites across 31 countries. Eligible patients were randomized 1:1 to sibeprenlimab 400 mg SC or PBO SC every 4 weeks for 26 doses. All patients from China included in the global main cohort who completed the 9-month uPCR-24h assessment were included. The primary endpoint is the ratio of uPCR-24h at 9 months compared with baseline. Secondary and exploratory endpoints include proteinuric remission (proportion of patients achieving urine total protein <0.5 g/d at 12 months), change from baseline in total serum IgA/IgG/IgM concentrations, and changes over time in spot uPCR, hematuria (dipstick), and free APRIL and serum galactose deficient (Gd)-IgA1 concentrations. Safety analyses included all randomized patients from China who received ≥1 dose of sibeprenlimab.

By the IA data cutoff, 42 patients from China (25 sibeprenlimab, 17 PBO) had completed the 9-month uPCR-24h assessment. Baseline characteristics for the China and global main cohorts were similar (Table 1). At 9 months, a reduction from baseline in uPCR-24 was observed in sibeprenlimab-treated patients (63.1%, 95% CI 52.1%-71.6%) vs PBO (3.1%, 95% CI -31.0% to 28.3%), corresponding to a PBO-adjusted reduction in uPCR-24h of 61.9% (95% CI 43.2%-74.5%). Similar to the global cohort, sibeprenlimab resulted in a rapid reduction in spot uPCR vs PBO that was evident at week 4 and sustained through week 40. Sibeprenlimab reduced serum IgA (-62.0%), IgG (-32.0%), IgM (-69.7%), and Gd-IgA1 (-65.6%) levels, and nearly completely suppressed APRIL levels (-95.8%); minimal changes were observed with PBO. Higher rates of proteinuric remission at 12 months and resolution of hematuria (dipstick negative) at week 48 were observed among patients treated with sibeprenlimab vs PBO (Table 2). TEAE incidence was comparable across the sibeprenlimab and PBO groups, with no deaths reported. In the sibeprenlimab group, no TEAEs led to treatment discontinuation, and no treatment-related serious TEAEs were reported (Table 3).

IA results for the China cohort of the VISIONARY trial were consistent with those previously observed in the IA of the global main cohort. Treatment with sibeprenlimab was associated with clinically meaningful reductions in proteinuria and biomarkers in patients with IgAN. Safety findings were comparable to placebo. Safety and the key secondary efficacy endpoint (eGFR slope) will be assessed at 24 months.