Takeda today announced positive results from its Phase 2b, randomized, 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 characterized by accelerated destruction of platelets, leading to decreased platelet counts and increased bleeding, which can be debilitating. These results (Abstract #LB 01.1) were presented at the oral Late-Breaking 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 ITP patients in the second half of FY2024.
The TAK-079-1004 trial (NCT04278924) evaluated three doses of subcutaneous mezagitamab (100mg, 300mg, and 600mg) versus placebo, administered once weekly for eight weeks in patients with chronic or persistent primary ITP, followed by more than eight weeks of safety follow-up. The primary endpoint was the percentage of patients with at least one Grade 3 or higher treatment-emergent adverse event (TEAE), serious adverse event (SAE), or adverse event (AE) 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 dose levels tested. Patients treated with mezagitamab showed rapid and sustained increases in platelet counts (above the 50,000/μL therapeutic threshold), which persisted eight weeks after the last dose through Week 16, illustrating the rapid and post-therapy effects of mezagitamab on platelet response.
The highest measures of platelet response were observed in patients treated with the 600mg dose of mezagitamab, with 81.8% achieving complete platelet response, 90.9% achieving clinically meaningful platelet response, and 100% achieving hemostatic platelet response. Fewer mezagitamab-treated patients had ≥1 disease activity-related bleeding AE compared to placebo (17.9% vs 46.2%).
“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, M.D., D.Phil., a leading ITP expert and study presenter at the ISTH oral Late-Breaking 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.”
In this study, mezagitamab had a favorable safety and tolerability profile in ITP patients, with no new safety signals and a safety profile consistent with prior studies. The rates of TEAEs leading to discontinuation, Grade >3 TEAEs, and SAEs between the mezagitamab dose groups combined versus placebo were 14.3% vs 0%, 17.9% vs 23.1%, and 14.3% vs 7.7%, respectively.
“It is a privilege to have these Phase 2b mezagitamab results selected for presentation as a late-breaking abstract at the ISTH Congress,” said Obi Umeh, M.D., M.Sc., Vice President, Franchise Global Program Leader at Takeda. “Based on these results, we plan to initiate a Phase 3 study of mezagitamab in ITP in the second half of FY2024, further underscoring our goal to develop transformative treatments in therapeutic areas with high unmet patient needs.”
About Mezagitamab Mezagitamab is a fully human immunoglobulin IgG1 monoclonal antibody (mAb) with high affinity for CD38-expressing cells (including plasmablasts, plasma cells, and natural killer cells), resulting in their depletion. Therapy with mezagitamab is designed to deliver rapid and sustained improvement in platelet response and restore platelet counts to functional levels.
Mezagitamab has received Orphan Drug Designation for the treatment of ITP and Fast Track Designation for the treatment of chronic/persistent ITP.
