Ianalumab Provides Clinical Benefit in Lupus Phase 2 Trial, With Ed Vital, MD

In an interview with HCPLive at ACR Convergence 2025 in Chicago, Ed Vital, MD, a translational medicine expert at the University of Leeds, discussed new phase 2 findings showing that ianalumab (VAY736), a next-generation B–cell–targeting antibody, achieved sustained lupus disease control and supported steroid tapering over 1 year.1

Ianalumab is a fully human monoclonal antibody targeting the BAFF receptor, designed to overcome limitations of earlier B cell therapies such as rituximab.2

“Ianalumab is a really interesting drug,” Vital said. “Ianalumab is a drug that targets B cells. Now, B cells as a target are not new. In fact, it's [been] about 20 years that we've started targeting them for depletion using rituximab, something I've worked on throughout my career, and one of the things I showed a long time ago is that the reason why rituximab doesn't work well enough for all patients is because it doesn't kill B cells completely—it reduces their number. We used to think they've all gone then we discovered that there are niches where they're hiding, and that's where the disease persists and comes back. So that's led to interest in developing…B cell depleting drugs that are more efficient.”

Vital explained that ianalumab has a dual mechanism of action, both B cell depletion and BAFF pathway blockade, which may account for its stronger and more durable effects.

Unlike rituximab’s lengthy infusions, ianalumab is given subcutaneously once a month and includes afucosylation, a structural modification that enhances antibody-dependent cell killing.

In a phase 2a randomized trial, 67 patients with active systemic lupus erythematosus (SLE) were randomized 1:1 to receive ianalumab 300 mg (n = 34) or to receive placebo (n = 33) and then ianalumab in the open-label phase. The study found that ianalumab 300 mg administered every 4 weeks produced notable efficacy over 52 weeks.1

At week 52, 38.2% of patients on continuous ianalumab achieved Lupus Low Disease Activity State (LLDAS) and 26.5% achieved remission (DORIS), compared with 21.2% and 12.1%, respectively, among those who began on placebo. Median time to first LLDAS was 40 weeks for the ianalumab arm.

The trial included a protocolized glucocorticoid taper, with 85.3% of patients on continuous ianalumab reducing their steroid dose to ≤5 mg after 52 weeks, compared with 72.7% of those switching from placebo. Patients on continuous ianalumab also spent a greater cumulative proportion of time in low disease activity, remission, and on lower steroid doses.

“Longer exposure to treatment led to not just response but…cumulative benefit of more time on target, and that starts to kick in the longer you spend on [the] drug,” Vital said. “This is a small study, and it's only a year duration, or just over a year, but [I] predict that bigger studies that had long-term extensions would translate into prevention of damage [and] better quality of life.”

Vital has no relevant reported disclosures.

References

1. Morand E, Gaillez C, Oliver S, Ghanshani S, Pozzobon M, Bao W, Vital E. Achieving Sustained Lupus Low Disease Activity State and Remission With Ianalumab (VAY736) in Patients with Systemic Lupus Erythematosus: A post hoc Analysis From a Phase II Study [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/achieving-sustained-lupus-low-disease-activity-state-and-remission-with-ianalumab-vay736-in-patients-with-systemic-lupus-erythematosus-a-post-hoc-analysis-from-a-phase-ii-study/. Accessed November 3, 2025.

2. Cuker A, Hanny Al-Samkari, Barcellini W, et al. Ianalumab, a Novel Anti-B-Cell Activating Factor (BAFF) Receptor (BAFF-R) Monoclonal Antibody (mAb) in Development for Immune Thrombocytopenia (ITP) and Warm Autoimmune Hemolytic Anemia (wAIHA), Has Demonstrated a Favorable Safety Profile in Sjögren’s Syndrome (SjS), Systemic Lupus Erythematosus (SLE) and Chronic Lymphocytic Leukemia (CLL). Blood. 2023;142(Supplement 1):5427-5427. doi:https://doi.org/10.1182/blood-2023-180055