Mezagitamab

---

The TAK-079 mechanism of action

Mezagitamab (TAK-079) is a human monoclonal antibody (human IgG1 lambda) that binds specifically to the CD38 transmembrane glycoprotein expressed on the surface of cells and can deplete those cells by distinct mechanisms.. Mezagitamab can induce apoptosis (i.e., programmed cell death) of cells which express a high density of the target antigen and/or recruit effectors of the immune system to lyse bound cells by complement-mediated cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis.. The sensitivity of cells to mezagitamab generally correlates positively with the density of CD38 molecules on the surface of the cell. Plasmablasts, plasma, and myeloma cells express the highest densities of CD38 and are most sensitive to mezagitamab; subsets of B, T, and natural killer cells express moderate densities of CD38 and are less sensitive to mezagitamab, whereas platelets and red blood cells express low densities of CD38 and are insensitive to mezagitamab.

Potential therapeutic utility of mezagitamab is being investigated in clinical trials of disorders caused by pathogenic CD38-expressing cells, such as multiple myeloma. Interim results of a clinical trial as a monotherapy for relapsed/refractory multiple myeloma demonstrated excellent safety and tolerability up through 1200 mg, the highest dose tested. No dose-limiting toxicities were observed, and a maximum tolerated dose was not identified. There were no infusion reactions, no drug-related serious adverse events, and two mild injection site reactions in more than 900 administrations. Mezagitamab demonstrated promising efficacy throughout this range of doses, with maximal benefit observed at 600 milligrams. The overall response rates were 56% and 33%; clinical benefit rates were 56% and 78%, respectively. The median progression-free survival was not estimable for the 600-milligram cohort, with a median FU of 6 months.. These clinical results are consistent with subcutaneous administration of the cytolytic CD38 antibody daratumumab to a similar population of relapsed/refractory multiple myeloma patients, except that daratumumab was administered at a higher dose (e.g., 1800 mg). This difference in potency, combined with an excellent safety profile, could benefit patients because mezagitamab might be self-administered using an injection device and not require a patient to travel to a treatment center for care, which could also reduce the overall cost of patient care for institutions and insurers.

The safety, pharmacokinetics, and pharmacodynamics of mezagitamab in combination with standard background therapy is being investigated in a clinical trial of patients with moderate to severe systemic lupus erythematosus because the antibody reduces the level of CD38-expressing cells associated with disease activity in laboratory experiments. In addition, mezagitamab was effective in an animal model of autoimmune disease, whereby it prevented arthritis as a prophylactic treatment and alleviated disease activity when administered therapeutically. The safe starting dose utilized in the first in human clinical trial was calculated by computer modeling of pharmacokinetic and pharmacodynamic data derived from these and additional laboratory studies.

The safety, tolerability, and efficacy of mezagitamab is also being investigated in a clinical trial of patients with myasthenia gravis and immune thrombocytopenia based upon the hypotheses that mezagitamab will reduce the levels of autoantibodies which are known to cause these autoimmune diseases. These hypotheses were derived from data demonstrating that a single dose of mezagitamab reduced levels of total IgA, IgG, and IgM, which are surrogate biomarkers of autoantibodies, in a clinical trial of healthy subjects.

This article "Mezagitamab" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Mezagitamab. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.

---