VAYHIT3: Ianalumab Reduces Bleeding, Depletes B Cells in Immune Thrombocytopenia, With Philip Choi, MBBS, PhD

Secondary analyses of the phase 2 VAYHIT3 trial support the efficacy profile of ianalumab, including rapid and profound B-cell depletion and reductions in bleeding events in heavily pretreated adults with primary immune thrombocytopenia (ITP).1

The data were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition by Philip Choi, MBBS, PhD, an associate professor at the Australian National University College of Science and Medicine.1

“VEHIT-3 is very much a proof-of-mechanism study. It wasn’t designed or powered to show superiority over other therapies. It was conducted in patients with severe, refractory ITP. These were predominantly older patients compared with typical first- or second-line ITP studies,” Choi said in an interview with HCPLive. “Despite that, and despite heavy prior immunosuppression, a meaningful proportion of patients derived significant benefit with very little toxicity. That’s the key message: BAFF receptor inhibitors may have an important role even for patients with very severe refractory ITP.”1

Ianalumab, a fully human IgG1 monoclonal antibody, is being investigated for its potential to treat various B cell-driven autoimmune diseases. The drug binds the BAFF receptor and depletes B cells through antibody-dependent cellular cytotoxicity while concurrently blocking BAFF.1,2

Primary analysis from VAYHIT3, a phase 2 open-label, single-arm study, was released earlier this year with a primary endpoint, confirmed platelet response (ConfR). The current analysis focuses on secondary outcomes, including the depth and duration of B-cell depletion, immunoglobulin trends, bleeding events, and safety. Responses assessed in the study included stable response (SR) and complete response (CR).1

The study enrolled adults with primary ITP and a platelet count <30 G/L, previously treated with at least a corticosteroid (CS) and a thrombopoietin receptor agonist.1

Upon analysis, Choi and colleagues observed rapid and potent B-cell depletion, with a median percent change from baseline of –97.6% before the 2nd infusion at week 5 and –99.9% before the 4th infusion at week 13. By the data cutoff, the median time to B-cell recovery was not estimable for investigators.1

Subgroup analysis of ConfR rates at week 25 suggested benefit across all subgroups, including 40% for patients with 2 to 3 prior treatments, 67% for 4 to 5, and 33% for ≥6 prior therapies; 42% for patients aged 18 to <65 years and 50% for those ≥65; and 48% of female patients versus 40% of male patients. The proportion of patients achieving CR increased from 10% at Week 9 to 22% at week 25.1

Investigators reported substantial reductions in both the number and severity of bleeding events. Post-baseline, all but 1 patient maintained IgG values ≥5 g/L. At study entry, 59% of patients reported bleeding events, with 44% grade 1. After the second infusion, bleeding events decreased substantially, and by week 25, 22% of evaluable patients reported any-grade bleeding, with 16% grade 1. No new safety signals emerged during longer follow-up.1

“We look forward to biomarker analyses over the next 12–18 months to help identify which patients are most likely to benefit from BAFF receptor inhibition,” Choi said. “Another open question is whether B-cell reconstitution will eventually lead to loss of response in some patients. Long-term data are still needed.”1

Editor’s Note: Choi reports relevant disclosures with Janssen Cilag, SOBI, Novartis, Amgen, and Sanofi.

References

1. Choi P, Bradbury C, Gonzalez-Lopez T, et al. Secondary analysis results from VAYHIT3, a phase 2 study of ianalumab in patients with primary immune thrombocytopenia previously treated with at least two lines of therapy. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Novartis ianalumab significantly extends disease control in patients with immune thrombocytopenia with only four once-monthly doses. Novartis. Published 2025. Accessed December 9, 2025. https://www.novartis.com/news/media-releases/novartis-ianalumab-significantly-extends-disease-control-patients-immune-thrombocytopenia-only-four-once-monthly-doses