Daratumumab is an investigational human IgG1k monoclonal antibody (mAb) that binds with high affinity to the transmembrane ectoenzyme, CD38, on the surface of multiple myeloma cells. It induces rapid tumor cell death through diverse mechanisms of action. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin's lymphoma.
Daratumumab has received Fast Track Designation and Breakthrough Therapy Designation from the US FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and IMiD. Breakthrough Therapy Designation is a program intended to expedite the development and review of drugs to treat serious or life-threatening diseases in cases where preliminary clinical evidence shows that the drug may provide substantial improvements over available therapy. Daratumumab has also received Orphan Drug Designation from the US FDA and the EMA for the treatment of multiple myeloma.
Daratumumab has multiple mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis and modulation of CD38 enzymatic activity. In pre-clinical studies, daratumumab has been shown to effectively kill multiple myeloma cells and to enhance the potency of other multiple myeloma treatments.
Genmab announced a global license and development agreement for daratumumab with Janssen Biotech, Inc. in August 2012. The agreement became effective in September 2012.
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