The addition of the investigational monoclonal antibody ianalumab to eltrombopag extended the time to treatment failure in patients with primary immune thrombocytopenia (ITP) after prior treatment with corticosteroids, according to findings from the phase III VAYHIT2 trial presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract LBA-2). Findings were also simultaneously published in The New England Journal of Medicine.
“As a hematologist, I’m glad that we have effective therapies for ITP, but they’re not necessarily ideal for chronic disease management or long-term quality of life,” stated lead report author Adam Cuker, MD, MS, Section Chief for Hematology, and Clinical Director of the Penn Blood Disorders Center. “This study shows that prolonged, durable responses to ITP treatment, without the need for ongoing therapy, are possible—and that’s a huge advantage for patients.” Hanny Al-Samkari, MD, presented the findings at ASH 2025.
Background and Study Methods
The randomized, double-blind, placebo-controlled phase III VAYHIT2 trial was created to explore the hypothesis that early intervention with ianalumab, a first-in-class monoclonal antibody that binds to and blocks the BAFF receptor, could reduce disease burden in a significant number of patients with ITP, as researchers believed that ianalumab would have disease-modifying effects.
The study enrolled adult patients with primary ITP who had an insufficient response to or relapse after corticosteroids in the first-line setting with or without intravenous immunoglobulins. All patients (n = 152) were randomly assigned to receive eltrombopag plus either ianalumab 9 mg/kg or ianalumab 3 mg/kg or placebo. In the three treatment arms, ianalumab or placebo were given as four once-a-month intravenous infusions in combination with daily eltrombopag for 16 weeks and then tapering off eltrombopag for 8 weeks.
Time to treatment failure was defined, for the purpose of the study, as time from randomization until platelet count was under 30 x 109/L or the start of rescue therapy 8 weeks after randomization, start of a new disease-related treatment, inability to taper or discontinue eltrombopag by week 24, or patient death.
Key Findings
Time to treatment failure, the primary endpoint, was significantly longer with the addition of ianalumab vs placebo: with ianalumab at 9 mg/kg, the hazard ratio (HR) was 0.55 (95% confidence interval [CI] = 0.32–0.92; log-rank P = .021), and with ianalumab at 3 mg/kg, the HR was 0.58 (95% CI = 0.34–0.98; log-rank P = .023). The median time to treatment failure was 13 months (95% CI = 5.1 months to not estimable) in the ianalumab 9 mg/kg arm, not estimable (95% CI = 3.7 months to not estimable) in the ianalumab 3 mg/kg arm, and 4.7 months (95% CI = 3.9–5.6 months) in the placebo arm.
Stable disease at 6 months was reached by 62% of patients in the 9 mg/kg ianalumab arm, 56.9% in the 3 mg/kg ianalumab arm, and 39.2% in the placebo arm. The 9 mg/kg vs placebo comparison achieved statistical significance with a P value of .023, but not did not for the 3 mg/kg vs placebo comparison (P = .035).
Platelet count response rates at 6 months were 73.5% with ianalumab at 9 mg/kg and 48% with placebo; platelet count complete response rates were 55.1% and 26%, respectively.
At the end of the tapering period for eltrombopag, patient-reported measurements for PROMIS short-form fatigue showed a greater reduction in fatigue in patients who received ianalumab at 9 mg/kg compared with those who received placebo (mean change from baseline = –7.7 vs –3.6).
All-grade adverse event rates were similar between the three treatment arms; grade 3 or higher adverse event rates were higher with the addition of ianalumab, at 24% in the 9 mg/kg arm and 20% in the 3 mg/kg arm, than the 3.9% rate seen in the placebo arm. Only one event of grade 1 palpitations was considered a serious drug-related adverse event. The rate and severity of infections was similar across all of the arms. Grade 3 or higher neutropenia was reported in 10% of patients in the ianalumab 9 mg/kg arm and in 4% in the ianalumab 3 mg/kg arm. No on-treatment adverse events led to ianalumab discontinuation, but one case was reported in the post-treatment period.
“We’re looking forward to seeing if the treatment-free responses in this study extend out even further,” Dr. Cuker said. “Improving the long-term reality of living with ITP is not something we’ve been able to think about before. The goal has always been to improve platelet counts or reduce the risk of bleeding, but this research is ushering in a new era of hope for patients with ITP.”
Disclosure: The study was funded by Novartis. For full disclosures of the study authors, visit hematology.org.
