OSAKA, JAPAN & CAMBRIDGE, MASS--(Business Wire / Korea Newswire)--Takeda (TSE:4502/NYSE:TAK) today presented 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 the accelerated destruction of platelets in blood, resulting in a decreased platelet count and an increase of bleeding that can be debilitating. These data (Abstract #LB 01.1) 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% achieved complete platelet response, 90.9% clinically meaningful platelet response, and 100% hemostatic platelet response.[1]
· Fewer mezagitamab-treated patients compared to placebo had ≥1 disease activity-related bleeding AE (17.9% vs 46.2%, respectively).[1]

“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 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.”

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% versus 0%, 17.9% versus 23.1%, and 14.3% versus 7.7% respectively.[1]

“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, 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 U.S. Food and Drug Administration. Mezagitamab is an investigational compound that has not been approved for use by any regulatory authority.

About the Mezagitamab Phase 2b Trial in ITP

The data presented at the ISTH oral Late-Breakthrough Session are from a pre-specified interim analysis of the Phase 2b trial, a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of mezagitamab in patients with persistent or chronic primary ITP. The trial had two parts: 25 participants were randomized (1:1:1) to mezagitamab 100mg or 300mg, or placebo in Part A while 16 participants were randomized (2:1) to mezagitamab 600mg or placebo in Part B. Participants received once weekly subcutaneous mezagitamab or placebo for 8 doses, followed by ≥8 weeks of safety follow-up.[1]

The primary endpoint is the percentage of patients with TEAEs including Grade 3 or higher events, SAEs and AEs leading to mezagitamab discontinuation. Secondary efficacy endpoints include and are defined as: platelet response (a platelet count ≥50,000/μL and ≥20,000/μL above baseline); complete platelet response (a platelet count ≥100,000/μL); clinically meaningful platelet response (a platelet count ≥20,000/μL above baseline); and hemostatic platelet response (participants with a baseline platelet count of