Novel, Fast-Acting Therapy Benefits Patients with Platelet Disorder in Phase 2 Trial

Key takeaways

• Approximately 20% of patients with immune thrombocytopenia previously had minimal benefit from current therapies
• Phase 3 trial underway with Mass General Brigham Cancer Institute as leading site

Results from a phase 2 clinical trial designed and overseen by researchers at Mass General Brigham Cancer Institute show that the investigational medication mezagitamab can effectively boost platelet counts in patients with immune thrombocytopenia (ITP), an autoimmune disease characterized by elevated platelet destruction and reduced platelet production that increases bleeding risk and compromises quality of life.

The findings, which are published in the New England Journal of Medicine, are especially meaningful given that approximately 20% of patients with ITP do not benefit from current therapies.

“This is a novel therapy that works fast and attacks the underlying mechanism of the disease,” said lead author David J. Kuter, MD, DPhil, a hematologist with Mass General Brigham Cancer Institute. “We saw that it can have a rapid effect, normalizing platelet counts in 48 hours and improving quality of life.”

Originally developed as a potential treatment for cancer, mezagitamab is an antibody that targets the CD38 protein expressed on the surface of various immune cells, especially plasma cells, as well as natural killer cells and certain T and B cells. Anti-CD38 therapy inhibits these immune cells, and its efficacy against autoimmune diseases shows potential.

In a phase 2 clinical trial sponsored by Takeda Development Center Americas, researchers tested mezagitamab’s potential against ITP. Investigators enrolled adults in Bulgaria, China, Croatia, Greece, Italy, Japan, Slovenia, Spain, and Ukraine with ITP that had persisted for at least three months. For the study, 41 participants were randomized to receive mezagitamab at a dose of 100 mg, mezagitamab at a dose of 300 mg, or placebo subcutaneously. After promising results from a safety analysis that was conducted after the trial was underway, participants were assigned in a 2:1 ratio to receive mezagitamab at a dose of 600 mg or placebo.

Treatment with mezagitamab led to increased platelet counts, with a safety profile similar to that of placebo. Through week 16, a platelet response was observed in 10-of-11 participants (91%) in the mezagitamab 600-mg group compared to 3-of-13 participants (23%) in the combined placebo groups.

“This study was designed as a dose-ranging, proof-of-concept trial. We are now conducting a phase 3 clinical trial of 600-mg dose of mezagitamab with Mass General Brigham Cancer Institute serving as the leading site in North America,” said Kuter.

Authorship: In addition to Kuter, co-authors include Katsuhiro Miura, Andrea Patriarca, Dražen Pulanić, Atanas Radinoff, Katya Sapunarova, Antonia Syrigou, Renchi Yang, Van Anh Nguyen, Emily Skelton, Scarlett Wang, Donald L. Yee, Parth Patwari, and Mezagitamab ITP Phase 2 Trial Investigators.

Disclosures: Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Funding: Supported by Takeda Development Center Americas.

Paper cited: Kuter D et al. “A Randomized Phase 2 Trial of Mezagitamab in Primary Immune Thrombocytopenia” NEJM DOI: 10.1056/NEJMoa2513120