The International Society on Thrombosis and Haemostasis (ISTH) 2025 Congress took place in Washington DC from 21-25 June 2025. At this event, Takeda presented final results from a Phase II trial evaluating mezagitamab (TAK-079), a potential best-in-class anti-CD38 monoclonal antibody (mAb), in patients with persistent or chronic primary immune thrombocytopenia (ITP). DDW’s Megan Thomas discussed these results and the future implications with data presenter Dr David Kuter, Director of Clinical Hematology at Massachusetts General Hospital.

ITP burden and clinical significance

Immune thrombocytopenia (ITP) is a rare but serious autoimmune condition where patients face low platelet counts, leading to bleeding risks, fatigue, and diminished quality of life. While current treatments are reasonably effective for many, around 20-30% of patients either do not respond or cannot tolerate them. As Dr Kuter highlights, these refractory patients are therefore in urgent need of new therapies.

Mezagitamab targets CD38, which is on the surface of plasma cells. Dr Kuter says: “So, this gives us a chance to target the underlying cause of the disease, not just make the platelet count higher, which is what other therapies for ITP tend to do.”

In a robust, placebo-controlled Phase II trial, mezagitamab was evaluated in patients with long-standing, severe ITP who had failed multiple prior therapies. The drug was administered weekly for eight weeks, followed by an eight-week monitoring period. The trial demonstrated that mezagitamab was highly safe, with adverse events mostly mild and similar across placebo and treatment arms.

Beyond lab values, mezagitamab also delivered meaningful improvements in patient-reported outcomes. All quality-of-life metrics improved in the treatment group, reaching clinically significant thresholds, while no such gains were seen in the placebo group. More details on the trial are available at www.takeda.com

Dr Kuter emphasises the significance of these findings. He says: “What I think is truly ‘unique’ about this study, and I say that with quotation marks around the word ‘unique’, is when one looks at quality of life issues. There are around 8-10 different parameters we checked in patients on the study, and all of the quality-of-life metrics increased in those who got mezagitamab, and none of those on placebo had an increase. So, basically, quality of life issues, which are increasingly important in ITP, responded quite nicely. In fact, they reached a minimum important difference, meaning they got above a threshold to be clinically relevant”.

In short, the results that Dr Kuter describes position mezagitamab as a promising new treatment option for patients with difficult-to-treat ITP.

Shaping treatment strategies

When asked how these results might shape the treatment strategies for chronic or persistent ITP going forward, Dr Kuter says the “honest answer” is that they can’t effect strategy until they have done a Phase III study. But, rephrasing the question, he says that if these results are validated, it could significantly impact how ITP is managed, particularly for patients with refractory disease, mirroring the population studied in clinical trials. He says: “A Phase III study that addresses the same patient population will, I hope, confirm these results that we’ve presented to you.”

Over time, as clinicians gain experience and confidence with the therapy, it may move into earlier lines of treatment, potentially becoming a second-line option. Given its rapid onset of action, there is also potential for it to be used earlier in the treatment course, possibly even upfront. However, Dr Kuter says this would require further studies, including trials in newly diagnosed patients.

Importantly, future research could explore whether early use of mezagitamab might prevent acute or persistent ITP from progressing to a chronic state, potentially reshaping the disease’s long-term trajectory. For now, though, its initial use would be reserved for patients who have failed existing second-line therapies.

Existing therapies

Dr Kuter explains that anti-CD38 antibodies, such as mezagitamab, target plasma cells. These are late cells in the immune system, which are known to produce the anti-platelet antibodies driving persistent ITP. He notes that analyses of spleens removed from patients who failed other therapies have revealed “a large concentration of plasma blasts or plasma cells in the spleen, that are making the anti-platelet antibody.” The goal, therefore, is to inhibit these cells and reduce antibody production.

However, what stood out in the trial was the speed of response, which suggests another mechanism may be at play. That means it’s not just targeting the plasma cells, but the acute response may be because this drug targets CD38 on what are called NK cells. Dr Kuter says: “This leads to an interesting observation that maybe NK cells play a major role in ITP.”

Comparing mezagitamab to the other studies, such as daratumumab or drug 313, Dr Kuter highlights that this trial’s placebo-controlled design adds critical context to the findings: “The placebo arm in this study — which is the important part, to be honest with you — illustrates the real dimension of the effect.” He concludes that the anti-CD38 treatment space is a novel and new therapy for ITP which is just beginning to be explored.

Broader development

In response to a questions regarding the broader development strategy for mezagitamab, particularly in light of recent IgAN data, Dr Kuter says that Takeda are currently focussing on CD38 in terms of immune cytopenias. He says: “ITP is the poster child for immune disorders, but this drug should have major effect in other autoimmune processes, such as in warm antibody haemolysis. There’s a whole spectrum of plasma cell or IgG mediated processes. This may play a major role and right now, this is only the beginning of a longer story.”

Looking forward

The first next step will be to conduct the Phase III study, showing the magnitude of the effect in a larger patient population. After that, Dr Kuter says a separate study in earlier disease patients may be necessary, to see that the drug acts quickly and possibly in patients within the first weeks or months of their IPT.

Dr Kuter outlines the typical development pathway for new ITP drugs, starting with Phase III trials in chronic patients, followed by studies in less severely affected individuals, and eventually long-term follow-up to assess sustained benefit. The key question, he says, is not whether a drug can cure ITP, but whether patients can be off the drug for months or years and have the disease not come back.

He emphasises the importance of evaluating durability of response, referencing rituximab in comparison; while it initially shows a 65% response rate, this drops to 40% at one year and just 21% at five years.

For mezagitamab, he stressed the need for similar long-term follow-up to determine whether it can deliver lasting remission by truly eliminating the plasma cells responsible for disease persistence.

In conclusion, mezagitamab represents a compelling and potentially transformative option in the ITP treatment landscape, particularly for patients with refractory disease. Its dual mechanism of action, targeting both plasma cells and possibly NK cells, may offer rapid and durable responses beyond those seen with existing therapies. While Phase III validation and long-term follow-up are still needed, early data from Takeda’s Phase II trial signal a meaningful advance in both efficacy and patient quality-of-life. As Dr Kuter says, this is “only the beginning of a longer story”; one that could ultimately redefine how immune cytopenias like ITP are understood and managed.

Biography

Dr David Kuter is Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School. A Harvard College graduate and Rhodes Scholar, he earned a DPhil in Biochemistry from Oxford and an MD from Harvard. Internationally recognised for his work on platelet biology, Dr Kuter has authored over 300 scientific papers, given over 500 invited lectures across 50 countries, and led numerous clinical trials that have helped shape modern haematology.