A Phase 2 Study of Ianalumab in Patients with Primary Immune Thrombocytopenia Previously Treated with at Least Two Lines of Therapy: Interim Results from VAYHIT3

Introduction: There is considerable unmet need for therapies for immune thrombocytopenia (ITP) that lead to sustained, safe platelet counts after treatment is discontinued. The B-cell activating factor (BAFF) signaling pathway is critically involved in B-cell proliferation, differentiation, and survival, making it an attractive therapeutic target. Ianalumab is an investigational, fully human anti-BAFF receptor (BAFF-R) monoclonal antibody; it has a novel dual mechanism of action, targeting B cells by BAFF-R signaling blockade and enhanced antibody-dependent cellular cytotoxicity (ADCC)-mediated B-cell depletion. Ianalumab has demonstrated promising efficacy and tolerable safety in several autoimmune diseases and is currently being investigated for the treatment of ITP. The VAYHIT3 study (NCT05885555) evaluates the safety and efficacy of ianalumab in patients with ITP previously treated with at least two lines of therapy. We present here the results of a protocol-planned exploratory interim analysis (IA) on the first 10 patients enrolled.

Methods: This Phase 2, open-label, single-arm study enrolled adult patients with primary ITP previously treated with at least a corticosteroid (CS) and a thrombopoietin receptor agonist (TPO-RA), and a platelet count <30 G/L. Patients with prior splenectomy were excluded. Eligible patients received four doses of ianalumab 9 mg/kg intravenously, one every 4 weeks; if clinically indicated, patients could continue concomitant therapy with CS and/or TPO-RA provided they were on a stable dose for at least 14 days before the first dose of ianalumab. The primary endpoint is confirmed response (ConfR), defined as a platelet count of ≥50 G/L at 2 or more consecutive assessments at least 7 days apart between Week 1 and Week 25, in the absence of rescue treatment for ≥4 weeks prior to platelet count assessment and start of new ITP treatment before reaching a ConfR. Secondary objectives include assessment of quality of response and safety. By the IA cutoff date (12 Jun 2024), 39 patients had been enrolled. This exploratory IA focuses on the first 10 patients who had completed the Week 25 visit or discontinued earlier by data cutoff.

Results: By data cutoff, 8 patients (80%) had completed the 4 infusions; 2 patients discontinued treatment early due to patient decision. Of the 2 patients who discontinued treatment, 1 remained in safety follow-up and 1 discontinued the study. Median (range) age was 55.5 (22‒72) years and 4 patients (40%) were male. Median (range) time from initial ITP diagnosis was 36.3 (3.9‒63.6) months, and median (range) baseline platelet count was 6.5 (1‒20) G/L. The majority of patients (6/10, 60%) had received ≥6 prior treatment regimens. Prior treatments included CS and TPO-RAs (all patients), rituximab (40%), and other immunosuppressants (60%). Overall, 8 patients received ianalumab together with a TPO-RA and 2 patients received ianalumab as monotherapy. Patients were followed for at least 6 months unless they had discontinued the study earlier.

By data cutoff, 5 patients (50%) had achieved ConfR. Four out of these 5 patients achieved ConfR within the first 8 weeks since the first infusion, of whom 3 patients had platelets ≥50 G/L without rescue or additional therapies by data cutoff. One patient achieved a transient (6 weeks) ConfR after Week 17. Among all 10 patients, median best post-baseline platelet count was 129.0 G/L (range, 3‒709 G/L).

During the treatment period, all 10 patients (100%) and 3 patients (30%) experienced any-grade adverse events (AEs) and Grade ≥3 AEs, respectively. Six patients had infections and 2 patients had infusion-related reactions; all of these events were Grade 1 or 2. No patients discontinued treatment due to AEs. After Week 25 there was one death due to pulmonary edema, which was assessed as unrelated to ianalumab. No safety signal was detected up to data cutoff.

Conclusions: These are the first ianalumab data in patients with primary ITP. The IA results on the first 10 patients enrolled in VAYHIT3 suggest that a short course of ianalumab shows promising efficacy and is well tolerated in heavily pretreated patients with ITP. These early interim results support the potential of ianalumab for addressing unmet medical need in primary ITP.