Trial drug mezagitamab boosts platelet in patients with immune thrombocytopenia

Phase 2 trial data have shown that the CD38-targeting antibody mezagitamab can rapidly restore platelet counts in immune thrombocytopenia, with strong response rates at higher doses and a safety profile comparable to placebo

A phase 2 clinical trial led by researchers at Mass General Brigham Cancer Institute, Boston, Massachusetts, USA, has reported that the investigational monoclonal antibody mezagitamab increased platelet counts in patients with immune thrombocytopenia, a chronic autoimmune disorder that combines accelerated platelet destruction with impaired platelet production and results in elevated bleeding risk and reduced quality of life.

The findings have added to the emerging evidence base for CD38-targeted therapies in autoimmune disease. The study addressed a clear unmet clinical need, as approximately one in five patients with immune thrombocytopenia do not achieve adequate disease control with existing therapeutic options.

“This is a novel therapy that works fast and attacks the underlying mechanism of the disease,” said Dr. David J. Kuter, lead author and haematologist at the Mass General Brigham Cancer Institute. 

“We saw that it can have a rapid effect, normalising platelet counts in 48 hours and improving quality of life,” he said.

Mezagitamab – which was originally developed as an anti-cancer agent – targets the CD38 surface protein expressed on multiple immune cell populations, including plasma cells, natural killer cells, and subsets of T and B lymphocytes. By inhibiting these cell types, anti-CD38 therapy aims to suppress pathological immune activity that drives platelet destruction in autoimmune thrombocytopenia. The approach reflects a broader shift in immunology to repurpose oncology-derived biologics for immune-mediated disorders.

The multicentre trial enrolled adults across several countries, including Bulgaria, China, Croatia, Greece, Italy, Japan, Slovenia, Spain, and Ukraine, all of whom had experienced persistent immune thrombocytopenia for at least three months. Investigators initially randomised 41 participants to receive subcutaneous mezagitamab at doses of 100 mg or 300 mg, or a placebo. Following an interim safety assessment conducted during the study, the protocol was amended to allocate subsequent participants in a 2:1 ratio to receive a higher 600 mg dose or placebo. The trial was sponsored by Takeda Development Center Americas.

Clinical outcomes indicated a clear dose–response relationship. Treatment with mezagitamab led to increased platelet counts across dosing cohorts, with the most pronounced effect observed in the 600 mg group. By week 16, 10 of 11 participants in this cohort, equivalent to 91 per cent, achieved a platelet response, compared with three of 13 participants, or 23 per cent, in the pooled placebo groups. The safety profile remained comparable to placebo, with no unexpected adverse events reported.

The rapid onset of action, with platelet normalisation observed within 48 hours in some cases, has highlighted the potential for mezagitamab to address both acute bleeding risk and longer-term disease burden. These findings have also reinforced interest in CD38 as a therapeutic target beyond oncology, particularly in conditions characterised by dysregulated humoral immunity.

“This study was designed as a dose-ranging, proof-of-concept trial. We are now conducting a phase 3 clinical trial of 600 mg dose of mezagitamab with Mass General Brigham Cancer Institute serving as the leading site in North America,” Kuter added.

The phase 3 programme has now been initiated and will aim to confirm efficacy and safety in a larger, more diverse patient population, as well as to assess durability of response and potential impact on bleeding outcomes and patient-reported quality of life.

For further reading please visit: 10.1056/NEJMoa2513120