Drug Overview
Isatuximab (Sanofi/ImmunoGen) is a humanized monoclonal antibody which targets cancer cells expressing the transmembrane glycoprotein CD38, which is highly expressed on malignant multiple myeloma (MM) cells, but at low levels in other tissues. Although the drug’s exact mechanisms of action are not fully understood, evidence indicates that it acts as an immune-modulatory agent that is able to activate natural killer cells and monocyte activation. By binding to CD38, myeloma cell death is induced by several different mechanisms, including apoptosis and antibody- and complement-dependent cytotoxicity.
Initial approvals in the relapsed/refractory settings would make isatuximab the second CD38-directed monoclonal antibody therapy to enter the market, and would place it in direct competition with more established therapies such as Darzalex (daratumumab; Johnson & Johnson), Farydak (panobinostat; Novartis), Kyprolis (carfilzomib; Amgen/Ono Pharmaceutical), Ninlaro (ixazomib; Takeda), and Pomalyst (pomalidomide; Celgene). Therefore, the author expects that isatuximab will initially be relegated to later lines of therapy. Ultimately, however, the drug is likely to gain the most uptake and maximize its commercial potential in the first-line setting, where it is being developed in combination with standards-of-care Velcade (bortezomib; Takeda/Johnson & Johnson), Revlimid (lenalidomide; Celgene), and dexamethasone for patients who are ineligible for stem cell transplantation (ClinicalTrials.gov identifier: NCT03319667).
Isatuximab (Sanofi/ImmunoGen) is a humanized monoclonal antibody which targets cancer cells expressing the transmembrane glycoprotein CD38, which is highly expressed on malignant multiple myeloma (MM) cells, but at low levels in other tissues. Although the drug’s exact mechanisms of action are not fully understood, evidence indicates that it acts as an immune-modulatory agent that is able to activate natural killer cells and monocyte activation. By binding to CD38, myeloma cell death is induced by several different mechanisms, including apoptosis and antibody- and complement-dependent cytotoxicity.
Initial approvals in the relapsed/refractory settings would make isatuximab the second CD38-directed monoclonal antibody therapy to enter the market, and would place it in direct competition with more established therapies such as Darzalex (daratumumab; Johnson & Johnson), Farydak (panobinostat; Novartis), Kyprolis (carfilzomib; Amgen/Ono Pharmaceutical), Ninlaro (ixazomib; Takeda), and Pomalyst (pomalidomide; Celgene). Therefore, the author expects that isatuximab will initially be relegated to later lines of therapy. Ultimately, however, the drug is likely to gain the most uptake and maximize its commercial potential in the first-line setting, where it is being developed in combination with standards-of-care Velcade (bortezomib; Takeda/Johnson & Johnson), Revlimid (lenalidomide; Celgene), and dexamethasone for patients who are ineligible for stem cell transplantation (ClinicalTrials.gov identifier: NCT03319667).
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