A Phase 2 Randomized Trial of Mezagitamab in Primary Immune Thrombocytopenia

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: 91% platelet response rate in 600mg group vs 23% in placebo

• Primary Outcome: Adverse events occurred in 68% mezagitamab vs 69% placebo groups

• Nnt Or Sensitivity: NNT approximately 1.5 for 600mg dose (based on 91% vs 23% response rates)

• Confidence Interval: Not reported in abstract

Clinical Application

Subcutaneous weekly administration is practical but requires 8-week treatment course Would require TGA approval and PBS listing consideration; fits treatment gap for refractory ITP patients currently managed with rituximab or splenectomy Adults with persistent/chronic ITP refractory to standard therapies, particularly those with severe thrombocytopenia

Abstract

BACKGROUND: Immune thrombocytopenia (ITP) is a disorder of increased platelet destruction and reduced platelet production and is associated with an increased bleeding risk and a compromised quality of life. Available therapies are ineffective in at least 20% of cases. Mezagitamab is an anti-CD38 antibody that targets plasma cells, plasmablasts, and natural killer cells. METHODS: We conducted this multicenter, double-blind, randomized, placebo-controlled trial to assess the safety and efficacy of mezagitamab at a dose of 100 mg, 300 mg, or 600 mg, as compared with placebo, administered subcutaneously once weekly for 8 weeks in adults with persistent or chronic ITP (mean platelet count on ≥2 measurements, <30,000 per microliter). The primary end point was adverse events. A key secondary efficacy end point was a platelet response (defined by a platelet count of ≥50,000 per microliter and ≥20,000 per microliter above the baseline value) on at least two visits at any time through week 16. RESULTS: In the combined mezagitamab groups (28 participants), the mean age was 50 years (range, 24 to 88) and the mean number of previous ITP therapies was 4 (range, 1 to 9); in the combined placebo groups (13 participants), the mean age was 39 years (range, 20 to 65) and the mean number of previous ITP therapies was 4 (range, 1 to 13). The mean baseline platelet count was 19,100 and 17,300 per microliter, respectively. Adverse events were reported in 19 of 28 participants (68%) in the combined mezagitamab groups and in 9 of 13 participants (69%) in the combined placebo groups; adverse events of grade 3 or higher in 5 of 28 participants (18%) and in 3 of 13 participants (23%), respectively; and serious adverse events in 4 of 28 participants (14%) and in 1 of 13 participants (8%). Through week 16, a platelet response was observed in 10 of 11 participants (91%) in the mezagitamab 600-mg group and in 3 of 13 participants (23%) in the combined placebo groups. CONCLUSIONS: Treatment with mezagitamab led to increased platelet counts, with a safety profile that appeared to be similar to that of placebo among participants with persistent or chronic ITP. (Funded by Takeda Development Center Americas; ClinicalTrials.gov number, NCT04278924.).

References

1. 1.Kuter, D. J., Miura, K., Patriarca, A., Pulanić, D., Radinoff, A., Sapunarova, K., Syrigou, A., Yang, R., Nguyen, V. A., Skelton, E., Wang, S., Yee, D. L., & Patwari, P. (2026). A Phase 2 Randomized Trial of Mezagitamab in Primary Immune Thrombocytopenia. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2513120