Ianalumab Shows Disease-Modifying Potential for Early ITP in the Phase 3 VAYHIT2 Trial

A late-breaking presentation at the American Society of Hematology (ASH) 2025 meeting revealed promising phase 3 findings for ianalumab, a first-in-class BAFF-receptor–blocking antibody designed to target B-cell dysfunction in immune thrombocytopenia (ITP).¹

In the VAYHIT2 trial (NCT05653219), early use of ianalumab combined with eltrombopag meaningfully extended time to treatment failure, increased stable response rates at 6 months, and supported successful tapering of eltrombopag—all without increasing infection risk. These results suggest ianalumab may offer a disease-modifying approach for patients who relapse after first-line steroids and are preparing to begin second-line therapy.

ITP is a rare autoimmune blood disorder in which the body’s immune system mistakenly attacks and destroys platelets, leading to a low platelet count and an increased risk of bruising and bleeding.² It can be acute and often resolves within a year, especially in children, or chronic, lasting longer and more commonly affecting adults. Symptoms vary from none at all to easy bruising, petechiae, nosebleeds, and heavy menstrual bleeding, and diagnosis typically involves excluding other causes of low platelets. Treatment depends on severity and may include steroids, intravenous immunoglobulin (IVIG) therapy, thrombopoietin‑receptor agonists, or other therapies to raise platelet counts and reduce bleeding risk.

The study evaluated ianalumab in adults with primary ITP who had an inadequate response to or relapsed after first-line corticosteroids, with or without IVIG therapy, and required second-line treatment.¹ Participants with platelet counts below 30×10⁹/L were randomized in a 1:1:1 ratio to receive eltrombopag plus either ianalumab 9 mg/kg, 3 mg/kg, or placebo. Ianalumab or placebo was administered as 4 monthly intravenous infusions alongside daily eltrombopag for 16 weeks, followed by an 8-week eltrombopag taper.

The study’s primary end point was time to treatment failure (TTF), while the key secondary end point assessed stable platelet response between weeks 19 and 25 without rescue therapy. Safety monitoring included adverse events through 28 days after the final infusion and extended evaluation of B-cell depletion–related events through study completion.

Adding ianalumab to eltrombopag significantly improved clinical outcomes for adults with primary ITP. TTF was prolonged with both ianalumab doses: the median TTF reached 13.0 months (HR, 0.55; 95% CI, 0.32-0.92; P = .021) with 9 mg/kg and was not estimable for 3 mg/kg compared with 4.7 months (HR, 0.58; 95% CI, 0.34-0.98; P = .023) for placebo. A stable response at 6 months was achieved by 62.0% of patients receiving 9 mg/kg and 56.9% receiving 3 mg/kg, vs 39.2% with placebo. At 6 months, response rates reached 73.5% with ianalumab 9 mg/kg compared with 48.0% with placebo, and complete response rates were 55.1% vs 26.0%, respectively.

Fatigue scores improved more with ianalumab, with a mean change of –7.7 vs –3.6 for placebo. Safety was comparable across arms, with all-grade adverse events reported in 84% to 94% of patients; notable events included grade 3 or greater neutropenia and infrequent mild infusion reactions. No increase in infection risk was observed.

By targeting the BAFF pathway, ianalumab in combination with eltrombopag not only prolonged time to treatment failure and improved 6-month stable platelet responses but also supported eltrombopag tapering and reduced fatigue—without increasing infection risk. These findings suggest that early intervention with ianalumab may provide a disease-modifying effect, potentially alter the natural course of ITP, and offer a meaningful advance for patients in need of effective second-line therapy.

References

1. Al-Samkari H, Cuker A, Zaja F, et al. Primary results from VAYHIT2, a randomized, double-blind, phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment. Presented at: ASH 2025; December 6-9, 2025; Orlando, Florida. Poster LBA-2

2. Immune thrombocytopenia (ITP). National Institutes of Health. Updated July 24, 2025. Accessed December 11, 2025. https://www.nhlbi.nih.gov/health/immune-thrombocytopenia