Mezagitamab Achieves Platelet Response, Favorable Safety in ITP Treatment

Mezagitamab (TAK-079) achieved positive results for patients with persistent or chronic primary immune thrombocytopenia (ITP) in a Phase 2b, randomized TAK-079-1004 study, according to late-breakthrough data presented at the 32nd Congress of the International Society on Thrombosis and Haemostasis (ISTH).¹

Announced on June 22, 2024, by Takeda Pharmaceuticals, patients with ITP treated with mezagitamab experienced rapid and sustained increases in platelet counts across all three dose levels, with a favorable safety profile in line with previous drug studies.

“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 presenter David Kuter, MD, DPhil, the director of clinical hematology at Massachusetts General Hospital and professor of medicine at Harvard Medical School.¹

ITP is a rare, IgG-mediated autoimmune disease caused by the development of autoantibodies to platelets and characterized by the accelerated destruction of platelets, resulting in a decreased platelet count and an increased risk of bleeding.² A precedent for approval of new drugs for ITP has been set, requiring platelet counts to be maintained at ≥50,000 µL for a sustained period.

Mezagitamab is a fully-human immunoglobulin IgG1 monoclonal antibody with a high affinity for CD83-expressing cells.¹ The therapy is designed to provide rapid, sustained improvement in platelet response and restore platelet counts to functional levels.

The US Food and Drug Administration (FDA) has previously granted mezagitamab Orphan Drug Designation for treating ITP and Fast Track Designation for treating chronic or persistent ITP.³

TAK-079-1004 assessed three dose cohorts of subcutaneous mezagitamab (100 mg, 300 mg, and 600 mg) versus placebo.¹ The drug was provided once weekly for 8 weeks in patients with chronic or persistent primary ITP and ≥8 weeks of safety follow-up.

Primary Phase 2b endpoints were the percentage of patients with ≥1 Grade 3 or higher treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to drug discontinuation. Secondary endpoints involved the platelet response, complete platelet response, clinically meaningful platelet response, and hemostatic platelet response.

These presented data were from a pre-specified interim analysis of the Phase 2b trial.

Treatment with mezagitamab improved platelet response, compared with placebo, across all three study dose cohorts. Patients demonstrated rapid and sustained increases above the 50,000/µL therapeutic threshold, which persisted 8 weeks after the last dose to Week 16 of the study.

The highest platelet response was identified among those treated with the mezagitamab 600 mg dose, with 81.8% achieving a complete platelet response, 90.9% showing clinically meaningful platelet response, and all patients exhibiting a hemostatic platelet response.

Safety of mezagitamab was favorable in ITP treatment, with no new safety signals identified, remaining consistent with previous data. Fewer patients treated with mezagitamab had ≥1 disease activity-related bleeding adverse event versus placebo-treated patients (17.9% vs. 46.2%).

Rates of TEAEs leading to discontinuation, Grade ≥3 TEAEs, and SAEs between the mezagitamab dose cohorts and placebo were 14.3% versus 0%, 17.9% versus 23.1%, and 14.3% versus 7.7%, respectively.

“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,” Kuter added.

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

“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,” said Obi Umeh, MD, MSc, vice president, franchise global program leader at Takeda.

References

1. _{Takeda unveils promising phase 2B results for Mezagitamab in treating primary immune thrombocytopenia. Takeda Pharmaceuticals: Global Homepage. June 22, 2024. Accessed June 25, 2024. https://www.takeda.com/newsroom/newsreleases/2024/late-breaking-data-from-phase-2b-study-of-mezagitamab/.}
2. _{Swinkels M, Rijkers M, Voorberg J, Vidarsson G, Leebeek FWG, Jansen AJG. Emerging Concepts in Immune Thrombocytopenia. Front Immunol. 2018;9:880. Published 2018 Apr 30. doi:10.3389/fimmu.2018.00880}
3. _{Search orphan drug designations and approvals. Mezagitamab. August 9, 2023. Accessed June 25, 2024. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=953823.}