Background
Phase 2, multicenter, double-blind, randomized, placebo-controlled dose-finding trial. 41 adults with persistent or chronic primary ITP (mean platelet count <30,000/mcL on ≥2 measurements). Mean number of prior ITP therapies: 4. Mezagitamab is a subcutaneous anti-CD38 antibody targeting plasma cells, plasmablasts, and NK cells — designed to deplete autoantibody-producing cells as a mechanism distinct from steroid-sparing or splenectomy. Three doses tested: 100 mg, 300 mg, 600 mg vs placebo.
Interventions and follow up
Arm A: Mezagitamab 100 mg, 300 mg, or 600 mg SQ once weekly x 8 weeks (n=28 combined)
Arm B: Placebo (n=13)
Primary endpoint: Adverse events (safety)
mFollow up: 16 week
Arm B: Placebo (n=13)
Primary endpoint: Adverse events (safety)
mFollow up: 16 week
Results
Platelet response (600 mg group): 91% (10/11) vs 23% (3/13) placebo through week 16
Platelet response (100 mg group): Not reported (lower efficacy at lower doses)
Platelet response (300 mg group): Not reported (intermediate dose)
Platelet response (100 mg group): Not reported (lower efficacy at lower doses)
Platelet response (300 mg group): Not reported (intermediate dose)
Adverse events
Main adverse events: Any-grade AEs 68% (mezagitamab) vs 69% (placebo). Grade ≥3 AEs 18% vs 23%. Serious AEs 14% vs 8%. No significant difference in adverse events between mezagitamab and placebo. Safety profile appeared similar to placebo.
Conclusions
Mezagitamab 600 mg achieved platelet responses in 91% of patients vs 23% with placebo in persistent/chronic ITP, with an acceptable safety profile similar to placebo. These results support further development of CD38-targeted therapy in ITP.
Key Limitations
Key Limitations: Very small sample size (41 total patients, 11 in the 600 mg group). Phase 2 dose-finding study — not powered for efficacy. Short follow-up (16 weeks) does not assess durability. Placebo group imbalance in baseline characteristics (younger, fewer prior therapies). Primary endpoint was safety, not efficacy. Larger phase 3 trial needed.
Clinical Context
ITP management in refractory or chronic disease remains challenging. Anti-CD38 targeting with daratumumab has shown activity in case series and small trials. Mezagitamab offers a subcutaneous, potentially more convenient anti-CD38 option. CD38 inhibition is mechanistically distinct from TPO-RAs (eltrombopag, romiplostim), anti-FcRn (efgartigimod, rozanolixizumab), and SYK inhibitors (fostamatinib), expanding the ITP armamentarium.
References
References: Kuter DJ et al, NEJM 2026 (mezagitamab phase 2)