Adding ianalumab to standard-of-care second-line eltrombopag prolonged the time to treatment failure vs placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) in the pivotal phase 3 VAYHIT2 study.

More patients treated with the novel, first-in-class monoclonal antibody were able to taper and discontinue eltrombopag — a thrombopoietin receptor agonist — and maintain safe platelet counts without the need for additional therapy, reported first author Hanny Al-Samkari, MD, at a late-breaking abstract session at American Society of Hematology (ASH) 2025 annual meeting.

The findings were published simultaneously in The New England Journal of Medicine.

“ITP is an autoimmune platelet disorder resulting in bleeding complications, constitutional symptoms, and significant negative impact on quality of life. Most adults presenting with newly diagnosed ITP will relapse following first-line corticosteroids and ultimately develop chronic disease,” said Al-Samkari, the Peggy S. Blitz endowed chair in hematology/oncology at Massachusetts General Hospital, and an associate professor of medicine at Harvard Medical School, Boston, at the meeting.

“These patients often require the indefinite administration of maintenance ITP therapies…to prevent bleeding and achieve satisfactory disease control,” he explained, noting that “the longer the duration of ITP, the more complex the autoimmune phenotype becomes and the more challenging the disease is to treat.”

To assess the potential for ianalumab — which targets B cells and processes that play a key role in primary ITP pathophysiology — to enable patients with ITP to discontinue therapy after a short course and maintain a response, the investigators randomized 152 patients in 1:1:1 fashion to receive four once-monthly infusions of 9 mg/kg ianalumab, 3 mg/kg ianalumab, or placebo. The eltrombopag was then tapered until discontinuation, and patients were followed for up to 2 years after the last dose of ianalumab or placebo.

Median time to treatment failure was 13.0 months, not reached, and 4.7 months in the 9 mg/kg, 3 mg/kg, and placebo groups, respectively (hazard ratios: 9 mg/kg, 0.55 and 3 mg/kg, 0.58).

Ianalumab also improved the rate of stable response at 6 months (SR6) — a key secondary study endpoint — with 62.0%, 56.9%, and 39.2% of patients in the groups, respectively, achieving SR6.

Significantly more patients in the ianalumab 9 mg/kg and 3 mg/kg groups vs the placebo group also achieved a response or complete response at 6 months, with 73.5%, 54.9%, and 48.0% achieving a response, and 55.1%, 40.0%, and 26.0% achieving a complete response, respectively.

Fatigue, a common symptom in patients with ITP, was significantly reduced after treatment tapering, particularly in patients in the 9 mg/kg group, Al-Samkari, noted.

The treatment was safe and well tolerated. No serious adverse events associated with ianalumab were observed, and no adverse events led to treatment discontinuation, he said, noting that infection severity and frequency were similar in the treatment and placebo groups.

“Longer-term follow-up is necessary to confirm the disease-modifying impact of ianalumab in primary ITP, and that follow-up is ongoing,” he concluded.

Ianalumab is also currently being investigated in the ongoing pivotal phase 3 VAYHIT1 study evaluating ianalumab and corticosteroids in the first line and the phase 2 study VAYHIT3 study in later lines for primary ITP.

Vinod A. Pullarkat, MD, applauded the investigators’ efforts and the “potentially practice-changing” findings.

Corticosteroids are given first-line but must be tapered within 4-6 weeks due to side effects. Those with insufficient response or relapse are then treated with second-line therapy, explained Pullarkat, a professor of hematology and hematopoietic cell transplantation at City of Hope, Duarte, California.

“The current landscape is that the second-line agents typically don’t do that much,” he added, noting they aren’t disease modifying. “They reduce the platelet count but don’t necessarily induce remission.”

“This trial is testing the idea that if you introduce a disease-modifying drug early in the course of disease, you can induce remission, and patients can be off therapy more often. Whether remissions will last for many years, we don’t know — but time off therapy is always good.”

The VAYHIT2 study was sponsored by Novartis Pharma AG, Basel, Switzerland. Al-Samkari disclosed relationships with numerous pharmaceutical companies, including Novartis. Pullarkat disclosed consulting and advisory roles with Novartis.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X @SW_MedReporter.