Takeda presented positive results from its Phase 2b, randomised, double-blind, placebo-controlled study evaluating the safety, tolerability and efficacy of mezagitamab (TAK-079) in patients with persistent or chronic primary immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder. ITP is characterised by the accelerated destruction of platelets in the blood, resulting in a decreased platelet count and an increase in bleeding that can be debilitating. These data were presented at the oral late-breakthrough session at the 32nd Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Bangkok, Thailand. Takeda plans to initiate a global Phase 3 trial of mezagitamab in patients with ITP in the second half of FY2024.
The TAK-079-1004 trial (NCT04278924) evaluated three different doses of subcutaneous mezagitamab (100mg, 300mg and 600mg) versus placebo, given once weekly for eight weeks in patients with chronic or persistent primary ITP, followed by >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.(2) Secondary endpoints included platelet response, complete platelet response, clinically meaningful platelet response, and hemostatic platelet response.(1,2)
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) (4), that persisted eight weeks after the last dose through to Week 16, illustrating the rapid and post-therapy effects of mezagitamab on platelet response. (1)
- All the different measures of platelet response evaluated were highest among patients treated with the mezagitamab 600mg dose, specifically 81.8 per cent achieved complete platelet response, 90.9 per cent clinically meaningful platelet response, and 100 per cent hemostatic platelet response. (1)
- Fewer mezagitamab-treated patients compared to placebo had ≥1 disease activity-related bleeding AE (17.9 per cent vs 46.2 per cent, respectively).(1)
In this study, mezagitamab had a favourable 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 per cent versus 0 per cent, 17.9 per cent versus 23.1 per cent, and 14.3 per cent versus 7.7 per cent respectively. (1)
About Mezagitamab
Mezagitamab is a fully human immunoglobulin IgG1 monoclonal antibody (mAb), 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 an Orphan Drug Designation for the treatment of ITP and Fast Track Designation for the treatment of chronic/persistent ITP from the US FDA. Mezagitamab is an investigational compound that has not been approved for use by any regulatory authority.
References:
- Kuter D, Pulanic D, et al. Safety, tolerability, and efficacy of mezagitamab (TAK-079) in chronic or persistent primary immune thrombocytopenia: Interim results from a phase 2, randomized, double-blind, placebo-controlled study. In: International Society on Thrombosis and Haemostasis (ISTH) Congress; June 22-26, 2024; Bangkok, Thailand. Abstract LB 01.1.
- https://clinicaltrials.gov/study/NCT04278924. Accessed June 2024.
- Provan D, Donald A, et al. Blood Advances. 2019;26;3(22):3780-3817.
- Rodeghiero F. International Journal of Hematology. 2023;117:316–33.