A database of FDA approved therapeutic peptides and proteins
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1724 details |
| Primary information | |
|---|---|
| ThPP ID | Th1174 |
| Therapeutic Peptide/Protein Name | Daratumumab |
| Sequence | NA view full sequnce in fasta |
| Functional Classification | IIIc |
| Molecular Weight | 148000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | Approximately 18 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 | Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Due to its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density. The FDA label recommends to defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed. Women of reproductive potential should also should use effective contraception methods during treatment and 3 months post-treatment to avoid pregnancy and exposure to the fetus while on daratumumab. |
| Metabolism | NA |
| Absorption | Following the recommended schedule and dose of 16 mg/kg, the mean serum Cmax value was 915 μg/mL at the end of weekly dosing, approximately 2.9-fold higher than following the first infusion. The mean predose serum concentration at the end of weekly dosing was 573 μg/mL. |
| Volume of Distribution | 4.7 L |
| Clearance | 171.4 mL/day. Clearance decreased with increasing dose and repeated dosing, indicating target-mediated pharmacokinetics. |
| Categories | Antineoplastic Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 |
| Information of corresponding available drug in the market | |
| Brand Name | Darzalex |
| Company | Janssen Biotech, Inc. |
| Brand Discription | DARZALEX is supplied as a colorless to pale yellow preservative-free solution for intravenous infusion in single-dose vials. The pH is 5.5. DARZALEX must be diluted with 0.9% Sodium Chloride Injection, USP |
| Prescribed for | DARZALEX is indicated 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 or who are double-refractory to a PI and an immunomodulatory agent. |
| Chemical Name | NA |
| Formulation | 100 mg/5mL |
| Physcial Appearnce | Solution, concentrate |
| Route of Administration | IV |
| Recommended Dosage | The recommended dose of DARZALEX is 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule. |
| Contraindication | The dose of DARZALEX at which severe toxicity occurs is not known. |
| Side Effects | Infusion reactions |
| Useful Link | http://www.rxlist.com/darzalex-drug.htm |
| PubMed ID | 28259300, 28205194, 28123899, 27195659, 26651519, 26362528, 24284914, 27363832, 27195659 |
| 3-D Structure | N.A. |