Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate (ADC) consisting of a humanized monoclonal IgG1 antibody conjugated through a protease-cleavable linker to monomethyl auristatin E (MMAE). The active substance has CAS No. 1313206-42-6 and FDA UNII KG6VO684Z6.
The EMA describes polatuzumab vedotin as an antibody-drug conjugate containing the polatuzumab antibody intermediate and the linker-drug vcMMAE. The conjugate has an average drug-to-antibody ratio (DAR) of 3.5, while its calculated molecular mass without C-terminal lysines and N-linked glycosylation is approximately 149,613 Da.
Polatuzumab vedotin combines three key components:
The linker-drug is attached to reduced interchain cysteine residues through thioether bonds. Following CD79b-mediated internalization, the linker is cleaved intracellularly and releases MMAE, which inhibits microtubules and causes death of dividing cells.
| Parameter | Details |
|---|---|
| Product Name | Polatuzumab Vedotin |
| Active Substance | Polatuzumab Vedotin |
| Synonym | Polatuzumab Vedotin-piiq |
| CAS Number | 1313206-42-6 |
| FDA UNII | KG6VO684Z6 |
| DrugBank | DB12240 |
| Molecular Type | Antibody-Drug Conjugate |
| Antibody Class | Humanized IgG1 monoclonal antibody |
| Target | CD79b |
| Cytotoxic Payload | Monomethyl Auristatin E (MMAE) |
| Linker | mc-vc-PAB |
| Average DAR | 3.5 MMAE molecules/antibody |
| Molecular Weight | Approximately 149.6 kDa |
| Calculated Molecular Mass | 149,613 Da excluding C-terminal lysines and N-linked glycosylation |
| Expression System | Chinese hamster ovary (CHO) cells for antibody component |
| Conjugation | Cysteine-based thioether conjugation |
FDA states that polatuzumab vedotin-piiq has an approximate molecular weight of 150 kDa and an average of 3.5 molecules of MMAE per antibody.
Polatuzumab vedotin is used as an antineoplastic antibody-drug conjugate for diffuse large B-cell lymphoma (DLBCL).
The EMA currently describes Polivy as indicated in combination with rituximab, cyclophosphamide, doxorubicin and prednisone for previously untreated adult DLBCL, and in combination with bendamustine and rituximab for certain adults with relapsed/refractory DLBCL who are not candidates for hematopoietic stem-cell transplantation.
The mechanism combines targeted CD79b binding with intracellular delivery of MMAE. After binding to CD79b on B cells, the ADC is internalized and the linker is cleaved, releasing MMAE to disrupt microtubule function and induce cell death.
Because polatuzumab vedotin is a complex biological ADC, conventional small-molecule tests such as melting point, residue on ignition and heavy metals are not appropriate primary release characteristics for the intact drug substance.
Important analytical characteristics include:
HIC is used to resolve DAR species, and published characterization work reports an average DAR of approximately 3.4–3.5.
Regulatory assessment documents also confirm that analytical methods for the drug substance are validated and that the manufacturing process includes conjugation, purification and formulation controls.
Polatuzumab vedotin is a specialized high-value biological ADC requiring controlled biotechnological and chemical manufacturing processes. Its production involves separate manufacture of the antibody and linker-drug components followed by controlled conjugation and purification.
For pharmaceutical development and manufacturing applications, documentation may include batch-specific analytical results, characterization data, stability information, technical documentation and regulatory-supporting documentation.
For the polatuzumab vedotin drug substance, regulatory assessment information supports storage at −20°C, with an accepted drug-substance shelf life of 36 months under the specified conditions.
This should not be confused with the finished Polivy drug product, which is stored at 2–8°C. The finished product is a lyophilized powder supplied in 30 mg and 140 mg vials.
Typical documentation for polatuzumab vedotin API may include:
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |