Drug intelligence / Profile preview

daratumumab + bortezomib + dexamethasone + dapagliflozin

Development stage
Unknown
Lead developer
Janssen Biotech
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Oral, Subcutaneous, Intravenous
01

Overview

This combination therapy, being investigated by Beijing Chao Yang Hospital, integrates the SGLT2 inhibitor dapagliflozin with the established D-Vd regimen (daratumumab, bortezomib, and dexamethasone) for the treatment of M-protein related cardiac disease, specifically cardiac amyloidosis. Daratumumab is a human IgG1k monoclonal antibody that targets CD38 on the surface of plasma cells, inducing cell death through multiple immune-mediated mechanisms. Bortezomib is a proteasome inhibitor that disrupts the degradation of intracellular proteins, leading to apoptosis in plasma cells. Dexamethasone is a potent glucocorticoid that provides synergistic anti-tumor activity and manages inflammation. Dapagliflozin is added to this backbone to provide cardioprotection and manage heart failure symptoms by inhibiting sodium-glucose cotransporter 2 (SGLT2) in the kidneys, which promotes diuresis and reduces cardiac preload and afterload. This multi-targeted approach aims to both eliminate the underlying clone responsible for amyloid production and support cardiac function in patients with significant cardiac involvement.

Other names
Dapagliflozin + D-VdD-Vd + DapagliflozinDaratumumab + Bortezomib + Dexamethasone + Dapagliflozin
02

Targets

GR (Glucocorticoid receptor)SGLT2 (Sodium-glucose cotransporter protein subunit 2)CD38 (Cluster of Differentiation 38)26S proteasome

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