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| Primary information |
|---|
| ID | 14196 |
| Therapeutic ID | Th1474 |
| Protein Name | Polatuzumab vedotin |
| Sequence | NA
|
| Molecular Weight | 149987 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The antibody conjugated monomethyl auristatin E has a terminal half life of 12 days.[Label] |
| Description | Polatuzumab vedotin is a CD79b specific antibody conjugated to the antineoplastic agent monomethyl auristatin E.[Label] This medication was granted accelerated FDA approval on 10 June 2019.[L6658] |
| Indication/Disease | This medication is indicated to treat adults with relapsed or refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab that has returned of progressed after 2 or more previous therapies.[Label] |
| Pharmacodynamics | The binding of the unconjugated drug to microtubules in B cells leads to a number of immunosuppressant adverse effects including neutropenia and thrombocytopenia.[Label,A179380] The incidence of peripheral neuropathy also increases with increasing doses and time exposed to the drug.[A179374] Polatuzumab vedotin does not prolong the QTc interval. |
| Mechanism of Action | Polatuzumab vedotin is an antibody targeted to CD79b conjugated to the antineoplastic agent monomethyl auristatin E (MMAE).[Label] The antibody binds to CD79b on the surface of B cells, causing the conjugate to be endocytosed.[Label] Once inside the cell, lysosomal proteases cleave the link between MMAE and the antibody allowing MMAE to bind to microtubules, inhibit cell division, and induce apoptosis.[Label] |
| Toxicity | Data regarding overdoses and LD50 are not readily available. In animal studies, embryo-fetal morality and birth defects were observed at less than the recommended dose and so the risk to the fetus must be weighed against the benefit to the mother.[Label] There is currently no data for the effects of polatuzumab vedotin on human pregnancies, though women are advised to used contraception while taking this medication.[Label] Women are advised not to breastfeed until 2 months after their last dose due to the potential risk to the infant, however no data is available regarding the effects of polatuzumab vedotin on the child or if it is present in breastmilk.[Label] Studies have not been performed to determine the carcinogenicity of this medication.[Label] Monomethyl auristatine E (MMAE) appears to be genotoxic in in vivo experiments but is not mutagenic in any tests performed.[Label] Based on animal data, polatuzumab vedotin may adversely affect male fertility and it is not known if this effect would be reversible.[Label] |
| Metabolism | The metabolism of polatuzumab vedotin has not been studied in humans but is likely to be catabolized to small peptides, amino acids, unconjugated monomethyl auristatin E (MMAE), and metabolites of MMAE.[Label] MMAE is metabolized by cytochrome P450 3A4.[Label] |
| Absorption | Antibody conjugated monomethyl auristatin E (MMAE) reaches a maximum concentration of 803±233ng/mL while unconjugated MMAE reaches a maximum concentration of 6.82±4.73ng/mL.[Label] The area under the curve for the conjugated medication is 1860±966day |
| The central volume of distribution is 3.15L.[Label] |
| Clearance | 0.9L/day.[Label] |
| Categories | Antineoplastic Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | B-cell antigen receptor complex-associated protein beta chain |
| Brand Name | Polivy |
| Company | Roche Registration Gmb H |
| Brand Description | Roche Registration Gmb H |
| Prescribed For | Intravenous |
| Chemical Name | 30 mg |
| Formulation | None. |
| Physical Appearance | low white blood cell count (neutropenia), low platelet count (thrombocytopenia), anemia, numbness and tingling of extremities, fatigue, diarrhea, fever, decreased appetite, pneumonia, vomiting, infusion site reactions, weight loss, and low blood potassium |
| Route of Administration | Polivy is used to treat diffuse large B-cell lymphoma after at least two other cancer treatments did not work or have stopped working. Polivy is given in combination with bendamustine (Bendeka, Treanda) and a medicine that contains rituximab (Rituxan). Polivy may also be used for purposes not listed... |
| Recommended Dosage | Polivy is a prescription medicine used to treat the symptoms of Diffuse Large B-Cell Lymphoma. Polivy may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate (ADC) consisting of three components: 1) the humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for human CD79b; 2) the small molecule anti-mitotic agent MMAE; and 3) a protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB) that covalently attaches MMAE to the polatuzumab antibody. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |