Primary information |
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ID | 10751 |
Therapeutic ID | Th1174 |
Protein Name | Daratumumab |
Sequence | >Th1174_Daratumumab
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Molecular Weight | 145391.7 |
Chemical Formula | C6466H9996N1724O2010S42 |
Isoelectric Point | NA |
Hydrophobicity | NA |
Melting point | NA |
Half-life | Intravenous daratumumab has a terminal half life of 18 ± 9 days.6 Subcutaneous daratumumab has a half life of 20 days |
Description | Daratumumab is an anti-cancer drug indicated for multiple myeloma in patients who have received at least 3 prior treatments. It was granted accelerated approval by the FDA in November 2016. Marketed under the brand name Darzalex by Janssen Biotech, daratumumab is the first monoclonal antibody injection approved for this indication and provides another options for patients with multiple myeloma resistant to other therapies. Daratumumab induces apoptosis of cancer cells by targeting the CD38 epitope, which is highly expressed on haematological malignancies. |
Indication/Disease | For the treatment of patients with multiple myeloma who have received at least three prior lines of therapy (a proteasome inhibitor (PI) and an immunomodulatory agent) or who are double-refractory to a PI and an immunomodulatory agent. This indication was approved by accelerated approval based on response rate. |
Pharmacodynamics | In preclinical trials, daratumumab showed synergistic activity with other multiple myeloma therapies, notably lenalidomide. Daratumumab also causes lysis in other cells that express CD38: myeloid-derived suppressor cells, a subset of regulatory T-cells, and NK cells. Decreases in absolute count and percentage of NK cells were observed during treatment. CD4+ and CD8+ T cell absolute counts as well the percentage of total lymphocytes increased in peripheral blood and bone marrow during daratumumab treatment. |
Mechanism of Action | Daratumumab is an immunoglobulin G1 kappa monoclonal antibody against CD38 antigen. CD38 is a transmembrane glycoprotein of many functions, including receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. CD38 is expressed on many cell types and tissues, and highly expressed in haematological malignancies including multiple myeloma tumor cells. By binding CD38, daratumumab causes inhibition of tumor cell growth and induces broad-spectrum apoptosis in multiple ways: by Fc-mediated cross linking, by immune-mediate tumor cell lysis through complement dependent cytotoxicity, antibody dependent cell cytotoxicity, and antibody dependent cellular phagocytosis. |
Toxicity | Data regarding overdoses of daratumumab are not readily available.[L13290,L13296] Patients should be treated with symptomatic and supportive measures.[L13290,L13296] |
Metabolism | Monoclonal antibodies are expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes.[A19126] |
Absorption | Subcutaneous daratumumab reaches a Cmax of 592µg/mL compared to intravenous daratumumab, which reaches a Cmax of 688µg/mL.[L13296] The AUC of subcutaneous daratumumab is 4017µg/mL |
| Daratumumab intravenous monotherapy has a volume of distribution of 4.7 ± 1.3L and the combination therapy has a volume of distribution of 4.4 ± 1.5L.[L13290] Subcutaneous daratumumab has a volume of distribution of the central compartment of 5.2L and a volume of distribution of the peripheral compartment of 3.8L.[L13296] |
Clearance | Intravenous daratumumab has a clearance of 171.4 ± 95.3mL/day.[L13290] Subcutaneous daratumumab has a clearance of 119mL/day.[L13296] |
Categories | Antineoplastic Agents |
Patents Number | NA |
Date of Issue | NA |
Date of Expiry | NA |
Drug Interaction | NA |
Target | ADP-ribosyl cyclase 1 |
Brand Name | NA |
Company | NA |
Brand Description | NA |
Prescribed For | NA |
Chemical Name | NA |
Formulation | 100 mg/5mL |
Physical Appearance | Solution, concentrate |
Route of Administration | IV |
Recommended Dosage | Injection |
Contraindication | NA |
Side Effects | NA |
Useful Link 1 | Link |
Useful Link 2 | NA |
Remarks | NA |