Ianalumab Improves Stable Response, Reduces Fatigue in ITP, With Hanny Al-Samkari, MD

When combined with eltrombopag, ianalumab prolonged time to treatment failure (TTF), improved stable response at 6 months (SR6), reduced fatigue, facilitated tapering off eltrombopag, and delayed need for subsequent therapy in patients with primary immune thrombocytopenia (ITP) who had previously received corticosteroids, according to the VAYHIT2 trial.1

ITP is an extremely common disorder, typically manifesting as bleeding. Its pathogenesis is highly complicated. ITP is caused by antibodies reacting to glycoproteins expressed on platelets and megakaryocytes, causing shortened survival of circulating platelets and impairing further production. Diminished numbers of regulatory T cells also contribute to its pathogenesis. While corticosteroids are the most common first-line therapy for ITP, they do not lead to durable remissions in most adults with ITP.2

Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, by Hammy Al-Samkari, MD, the Peggy S. Blitz Endowed Chair in hematology and oncology at the Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, these data mark the second of 3 phase 3 studies in the VAYHIT program, evaluating the efficacy and safety of ianalumab.1

“This is a very potent agent, a BAFF receptor inhibitor, that has a dual mechanism of action – it very potently depletes B cells and prevents the maturation and differentiation of new B cells,” Al-Samkari told HCPLive in an exclusive interview. “This is of significant potential in a disease driven by autoreactive B cells, particularly when given early in the course of the disease.”

VAYHIT2 was a randomized, double-blind, placebo-controlled phase 3 study. It included patients who had insufficient response to or relapse after first-line corticosteroid therapy (+/0 intravenous immunoglobulin), a platelet count <30x109/L, and were naïve to and had an indication for second-line ITP treatment. Patients were randomly assigned in a 1:1:1 ratio to eltrombopag plus either ianalumab 9 mg/kg or 3 mg/kg, or placebo. Ianalumab and placebo were delivered as 4 once-monthly intravitreal infusions with eltrombopag for 16 weeks, followed by an 8-week eltrombopag tapering period.1

The study’s primary endpoint was TTF, which was defined as time from randomization until platelet count reached <30x109/L or start of rescue therapy 8 weeks after randomization, start of a new ITP therapy, inability to taper or discontinue eltrombopag by week 24, or death. The key secondary endpoint was SR6, defined as having ≥75% of platelet counts between weeks 19 and 25 being ≥50x109/L without rescue or new ITP treatment.1

Ultimately, 152 patients were enrolled in the trial – 50 were assigned to ianalumab 9 mg/kg, 51 to ianalumab 3 mg/kg, and 51 to placebo. The median follow-up period was 12.9 (interquartile range [IQR], 8.6-18), 13.6 (8.4-18.1), and 11.6 (8.1-18.2) months in the 9 mg/kg, 3 mg/kg, and placebo arms, respectively. TTF was substantially longer with ianalumab 9 mg/kg (HR 0.55; 95% CI, 0.32-0.92; log-rank P = .021) and ianalumab 3 mg/kg (HR, 0.58; 95% CI, 0.34-0.98; log-rank P = .023) compared with placebo.1

Additionally, substantially more patients achieved SR6 with ianalumab 9 mg/kg (n = 31) versus placebo (n = 20). At the end of the eltrombopag tapering period, fatigue reduction was -7.7 for ianalumab 9 mg/kg and -3.6 for placebo. All grade adverse events were also similar between arms, with grade ≥3 events occurring in 12, 10, and 2 patients in the 9 mg/kg, 3 mg/kg, and placebo arms, respectively. Grade ≥3 neutropenia occurred in 5 and 2 patients in the 9 mg/kg and 3 mg/kg arms, respectively, and no on-treatment events led to ianalumab discontinuations.1

Ultimately, Al-Samkari and colleagues determined that ianalumab, when combined with eltrombopag, efficaciously reduces fatigue, facilitates tapering off eltrombopag, prolonged TTF, improved SR6, and delayed the need for subsequent therapy. It was well tolerated with no observed increase in infection risk versus placebo.1

“The remaining question, which we will answer with long-term follow-up, is whether ianalumab will be disease-modifying in addition to providing a long duration of treatment-free response,” Al-Samkari said. “Will it allow patients who would have otherwise progressed to a more severe chronic course to have a milder course? That’s something we’re still looking to answer.”

Editor’s Note: Al-Samkari reports disclosures with Pharmacosmos, Agios, Amgen, Vaderis, Novartis, Sobi, and others.

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. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Kistangari G, McCrae KR. Immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3):495-520. doi:10.1016/j.hoc.2013.03.001