Mezagitamab (TAK-079): A Comprehensive Report on an Investigational Anti-CD38 Monoclonal Antibody

1. Executive Summary

Mezagitamab (TAK-079) is an investigational, fully human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody targeting the CD38 protein. It is being developed primarily by Takeda, following its initial discovery using BioInvent's n-CoDeR® platform, for the treatment of various autoimmune diseases and hematologic malignancies where CD38-expressing cells play a pathogenic role. The drug is administered via subcutaneous injection.

The primary mechanism of action involves binding to CD38 on the surface of plasmablasts, plasma cells, Natural Killer (NK) cells, and activated T and B lymphocytes. This binding leads to the depletion of these cells through multiple effector functions, including Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC), and allosterically inhibits the enzymatic activity of CD38.

Mezagitamab's most advanced clinical program is for Primary Immune Thrombocytopenia (ITP). Positive topline results from the Phase 2b trial (NCT04278924) demonstrated dose-dependent, rapid, and sustained platelet responses, prompting progression to a global Phase 3 trial (NCT06722235). The drug is also under investigation for Myasthenia Gravis (Phase 2 completed with some positive signals), Relapsed/Refractory Multiple Myeloma (Phase 1b showing promising activity), Systemic Lupus Erythematosus (Phase 1b/2 with modest clinical efficacy despite pharmacodynamic effects), and IgA Nephropathy (Phase 1/2 ongoing).

Across various studies, mezagitamab has generally been reported as well-tolerated, with a manageable adverse event profile. The subcutaneous route of administration and a potentially favorable safety profile, particularly concerning infusion-related reactions and certain hematologic toxicities compared to some intravenous anti-CD38 therapies, are notable features.