Interim safety and efficacy of subcutaneous (S.C.) Dose ianalumab (vay736; anti-baff-r mab) administered monthly over 28 weeks in patients with systemic lupus erythematosus (SLE).

Abstract

Background Ianalumab (VAY736; defucosylated, human IgG1 anti-BAFF-receptor mAb), provides both antibody-dependent cellular cytotoxicity-mediated B cell depletion and BAFF-receptor signaling blockade. We report here ianalumab safety and efficacy in patients with active SLE. Methods Placebo-controlled, randomized, parallel group, double- blind treatment cohort within a multi-center platform trial. Patients with ANA >=1:80 and meeting >=4/11 ACR 1997 SLE classification criteria, with SLEDAI-2K score >=6 and BILAG- 2004 >=1A or >=2B, including activity in either mucocutaneous and/or musculoskeletal domains were enrolled. We report interim analysis for the first 48 patients enrolled into the ianalumab- treatment cohort (active=22, placebo=26) completing the 28-week (w) blinded treatment period, comprised of ianalumab 300mg or placebo monthly s.c. injections. Outcomes were measured at baseline and every 4w till w28. Primary outcome was proportion patients meeting composite endpoint: achieving w28 SRI-4 and tapering predniso(lo)ne to 5 mg/d or baseline dose, whichever was lower, by w16 and remaining so to w28. Secondary/exploratory outcomes included safety, incidence moderate/severe flare (BILAG-2004 >=1A or >=2B), LLDAS, SLEDAI-2K, BILAG-2004, and physician/patient global VAS. Results Ianalumab was safe/well-tolerated with no drug-related SAE or dropouts and one pandemic-related discontinuation in placebo arm. Mean age=40y; 7 males (placebo=5, ianalumab= 2). Baseline mean(range) for ianalumab and placebo was: SLEDAI-2K, 12.4(6 32) and 11.6(4 21), and predniso(lo)ne 11.3mg(3 30) and 11.4mg(3 28). Proportion ianalumab or placebo patients achieving w28 SRI-4 (figure 1) was 77.3% (n=17) vs. 26.9% (n=7), and also meeting composite endpoint: 54.5%(n=12) vs. 11.5%(n=3). Proportion with moderate or severe flare were 40.9% (ianalumab, n=9) vs. 65.4% (placebo, 17). Ianalumab also showed treatment benefit vs placebo in time-to-moderate or severe flare and achieving w28 LLDAS. Conclusions Treatment of SLE with ianalumab was safe, well tolerated, and more patients achieved composite primary endpoint SRI-4 with sustained steroid reduction vs. placebo arm, with other evidence for clinical improvement, including reductions in moderate/severe flares and LLDAS.