Ianalumab in patients with systemic lupus erythematosus: Interim results of a phase II trial

Ianalumab (VAY736), an afucosylated human immunoglobulin G1 monoclonal antibody targeting the B-cell activating factor receptor (BAFFR), is a novel therapeutic agent for systemic lupus erythematosus (SLE) which depletes B cells through enhanced antibody-dependent cellular cytotoxicity and concurrent BAFF:BAFFR blockade.^1,2

Below, we summarize the interim findings from a phase II trial (NCT03656562) evaluating ianalumab in patients with SLE, presented by Shen et al.¹ and Santos da Costa et al.² at the American College of Rheumatology (ACR) annual meeting (ACR Convergence 2023).

Study design

This was a multicenter, randomized, double-blind placebo-controlled trial. The study design is depicted in Figure 1.

ANA, antinuclear antibody; BILAG, British Isles Lupus Assessment Group; d, day; IV, intravenous; MP, methylprednisolone; PI, principal investigator; q4W, every four weeks; SC, subcutaneous; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; SoC, standard of care; W, week.
*Adapted from Shen, et al.^1
†Or <baseline, whichever is lower.

Key findings^1,2

In total, 34 patients (median age, 42 years) were treated with ianalumab and 33 (median age, 39 years) were treated with placebo; 94.1% and 81.8% were female, respectively.¹

Treatment with ianalumab resulted in:

• higher proportion of patients achieving SLE Responder Index-4 response with sustained steroid reduction (primary composite endpoint) and Lupus Low Disease Activity State, and reduced incidence of moderate or severe flare (Figure 2A).¹
• substantial and significant reduction in total B cells, including naïve and memory B cells, and antibody-producing subsets, while preserving levels of CD4⁺ and CD8⁺ T cells or natural killer cells.²
• strong reduction in B-cell-related genes, a trend for downregulation of interferon gene signature,² and an acceptable safety profile (Figure 2B).¹

AE, adverse event; LLDAS, Lupus Low Disease Activity State; SAE, serious AE; SRI-4, Systemic Lupus Erythematosus Responder Index-4; W, week.
*Adapted from Shen et al.^1
†All events occurred before the first administration of open-label treatment.

Key learnings

Preliminary phase II data showed that ianalumab was well tolerated, effectively depleted B cells, achieved the primary composite endpoint, and demonstrated beneficial effects across other study measures. The results support the ongoing phase III trials of ianalumab in patients with: systemic lupus erythematosus (SIRIUS-SLE 1, NCT05639114; SIRIUS-SLE 2, NCT05624749); and lupus nephritis (SIRIUS-LN, NCT05126277).