At the ASH 2025 Annual Meeting & Exposition, Hanny Al-Samkari, MD, Harvard Medical School, Boston, Massachusetts, presented a late-breaking abstract on phase 3 data from the randomized, double-blind, placebo-controlled VAYHIT2 study on ianalumab vs placebo added to standard-of-care eltrombopag as second-line treatment for patients with primary immune thrombocytopenia (ITP) who had insufficient response to/relapse after first-line corticosteroid therapy. 

Patients saw improved time-to-treatment failure, improved platelet responses, and improved rates of fatigue as well as favorable safety with ianalumab versus placebo. 

"We really hope to shake up the treatment paradigm in the treatment of ITP," Al-Samkari stated. 

Transcript:

Hi, I'm Hanny Al-Samkari. I'm a classical hematologist and clinical investigator, the Peggy Blitz Endowed Chair in Hematology-Oncology at Massachusetts General Hospital/Mass General Brigham, and an associate professor of medicine at Harvard Medical School. 

It's my pleasure to talk about VAYHIT2, which is one of the late breaking abstracts at ASH. VAYHIT2 is a pivotal phase 3 randomized placebo controlled trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with pure second-line ITP. In other words, these are patients early in the disease course who have progressed past first-line corticosteroids, but have not yet received other second-line therapies. This is a novel approach to a clinical trial in ITP because it's evaluating adding a very potent immune-acting medication early on in the disease course. So ianalumab is an antibody with a dual mechanism of action.

It both functions as a very potent B-cell depletor, and it blocks the BAF receptor signaling and BAF receptor is the B-cell activating factor. Blocking the signaling is very important in preventing the maturation and differentiation of new B-cells that can be autoreactive and perpetuate the autoimmune response in ITP. And so, what this study was seeking to evaluate was what was the difference in time to treatment failure between standard of care eltrombopag alone versus adding ianalumab to standard of care? 

The study was positive. It showed that adding ianalumab early on in the disease course provided for a nice duration of durable response. In patients with ITP, meaning they had no requirement for treatment. All patients in the study had a taper of their eltrombopag completed by 6 months. So patients receiving ianalumab, either low dose ianalumab or higher dose ianalumab because there were 3 arms, 2 ianalumab arms, and 1 placebo arm had significant improvements in time to treatment failure. It was 13 months in the high dose ianalumab arm, not yet reached in the low dose ianalumab arm, and 4.7 months in the placebo arm. All of the other secondary end points that were evaluated in the study, including platelet response rates and fatigue, were all directionally improved in patients receiving ianalumab versus placebo. 

This was a very unique way of approaching a new medication in ITP because rather than looking at simply platelet response, 4 out of 6 for the last 6 platelet counts above 50,000, for example, it really looked at something that is clinically relevant: time to treatment failure. How long can we keep patients with ITP off of a chronic therapy when giving them an episodic therapy upfront? And very importantly, ianalumab did this very safely, right? 

The adverse event profile was quite favorable. There was no increase in frequency or severity of infections in either of the ianalumab arms relative to placebo. The main adverse event that was seen more frequently in patients receiving ianalumab was transit neutropenia. And when I say transient, I mean days to a couple of weeks, right? Not clinically relevant. Did not translate to increased rates of infections or severity of infections. 

The main follow-up that is currently ongoing in this study is seeking to answer the third question, the first being, is it efficacious in giving that long duration free response or long treatment free response? It is, is it safe in doing that? It is. The third question is, is this disease modifying for ITP? Because the average duration of disease in patients who were enrolled in the study was around 3 to 4 months. They had not had very long disease. And so we know that the longer people go with ITP, the more complex their autoimmune response becomes, the more challenging the disease becomes to treat. There's more people develop oligoclonal T-cell clones that make the disease very, very challenging to manage. 

Can we defang the disease by intervening early with a very potent agent? That is sort of the cherry on top kind of question. We know the drug is safe and effective—but will it also have this additional benefit? We're going to answer that over the follow-up, which is coming over the next 2 years. This study is following patients for over 3 years after the last patient is randomized. 

This is also just part of a clinical trial program in ITP with ianalumab, and there's another pivotal phase 3 called VAYHIT1, which is evaluating ianalumab in combination with corticosteroids in the first-line, again with many of the same goals. So a different way of approaching ITP, but certainly a clinically relevant one. We really hope to shake up the treatment paradigm in the treatment of ITP.
 

Source:

 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. Dec 6-9, 2025; Orlando, FL. Abstract: LBA-2