Takeda Presents Positive Phase 2b Results in ITP

Rare Daily Staff

Takeda presented positive results from its phase 2b study of mezagitamab in patients with persistent or chronic primary immune thrombocytopenia, a rare immune-mediated bleeding disorder.

Takeda plans to initiate a global Phase 3 trial of mezagitamab in patients with ITP in the second half of 2024.

Primary immune thrombocytopenia (ITP) is a rare, IgG mediated autoimmune disease caused, in part, by the development of autoantibodies to platelets (and/or megakaryocytes), which are blood components responsible for preventing or stopping bleeding. It is characterized by the accelerated destruction of platelets (with or without impaired production), resulting in a decreased platelet count and an increased risk of bleeding, which can be debilitating (including fatigue and impaired quality of life), and in severe cases may be life-threatening.

The precedent for approval of new drugs in ITP requires that platelet counts be maintained at 50,000/uL or more for a sustained period. Approximately 20 percent of patients with ITP do not achieve a platelet count above 50,000/uL following treatment with available first- and second-line therapies creating significant patient burden and unmet need for a disease modifying treatment that is also tolerable.

Mezagitamab is a fully human immunoglobulin IgG1 monoclonal antibody with high affinity for CD38 expressing cells (including plasmablasts, plasma cells, natural killer cells), resulting in their depletion. Therapy with mezagitamab is designed to deliver rapid and sustained improvement in platelet response and to restore platelet counts to functional levels.

Mezagitamab previously received Orphan Drug designation for the treatment of ITP and Fast Track designation for treatment of chronic/persistent ITP from the FDA.

The data were presented at the oral Late-Breakthrough Session at the 32nd Congress of the International Society on Thrombosis and Haemostasis in Bangkok, Thailand.

The TAK-079-1004 trial evaluated three different doses of subcutaneous mezagitamab versus placebo, given once weekly for eight weeks in patients with chronic or persistent primary ITP, followed by greater than 8 weeks of safety follow-up. The primary endpoint is the percentage of patients with at least one Grade 3 or higher treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to mezagitamab discontinuation. Secondary endpoints included platelet response, complete platelet response, clinically meaningful platelet response, and hemostatic platelet response.

The Phase 2b trial results demonstrated that mezagitamab treatment improved platelet response compared to placebo, across all three dose levels of mezagitamab tested. Patients treated with mezagitamab showed rapid and sustained increases in platelet counts (above the 50,000/μL therapeutic threshold), that persisted eight weeks after the last dose through to Week 16, illustrating the rapid and post-therapy effects of mezagitamab on platelet response.

All the different measures of platelet response evaluated were highest among patients treated with the mezagitamab 600mg dose, specifically 81.8 percent achieved complete platelet response, 90.9 percent clinically meaningful platelet response, and 100 percent hemostatic platelet response.

Fewer mezagitamab-treated patients compared to placebo had ≥1 disease activity-related bleeding AE (17.9 percent vs 46.2 percent, respectively).

In this study, mezagitamab had a favorable safety profile in patients with ITP, with no new safety signals and consistent with prior studies of mezagitamab.1 The rates of TEAEs leading to discontinuation, Grade >3 TEAEs, and SAEs, between the mezagitamab dose groups combined versus placebo were 14.3 percent versus 0 percent, 17.9 percent versus 23.1 percent, and 14.3 percent versus 7.7 percent respectively.

“Despite treatment with currently available therapies, there is still a significant disease burden and need for a disease modifying treatment that people living with ITP can tolerate,” said David Kuter, a leading expert in ITP and study presenter at the ISTH oral Late-Breakthrough Session. “These phase 2b trial results are especially encouraging because they show mezagitamab’s favorable efficacy and safety profile – setting the stage for the generation of additional clinical evidence for this anti-CD38 monoclonal antibody with best-in-class potential for efficacy in ITP.”