Gemtuzumab Ozogamicin is a recombinant antibody-drug conjugate (ADC) consisting of a humanized anti-CD33 monoclonal antibody linked to the cytotoxic agent N-acetyl gamma calicheamicin. It is designed to selectively deliver the cytotoxic payload to CD33-expressing cells, particularly leukemic myeloid cells.
Gemtuzumab Ozogamicin is marketed as MYLOTARG and is used in the treatment of CD33-positive acute myeloid leukemia (AML). FDA records document its approval for newly diagnosed CD33-positive AML and for relapsed or refractory CD33-positive AML in adults and appropriate pediatric patients.
Unlike conventional small-molecule APIs, Gemtuzumab Ozogamicin is a complex biological conjugate. The drug substance consists of conjugated and unconjugated antibody molecules with varying numbers of calicheamicin derivative molecules attached. Current FDA labeling describes an average of approximately 2–3 calicheamicin derivative molecules per antibody molecule, with individual conjugates ranging predominantly from zero to six.
The antibody component is a recombinant humanized IgG4 kappa monoclonal antibody, produced using mammalian cell culture, and is directed against the CD33 antigen. The cytotoxic calicheamicin derivative causes DNA damage after intracellular release, ultimately resulting in cell death.
| Property | Value |
|---|---|
| API Name | Gemtuzumab Ozogamicin |
| CAS Number | 220578-59-6 |
| UNII | 8GZG754X6M |
| Development Code | CMA-676 / CMC-676 |
| Brand | MYLOTARG |
| Biological Class | Antibody-Drug Conjugate (ADC) |
| Antibody Type | Recombinant Humanized IgG4 Kappa |
| Target | CD33 |
| Cytotoxic Payload | N-acetyl gamma calicheamicin |
| Average Drug-to-Antibody Ratio | Approximately 2–3 |
| Molecular Weight | Approximately 151–153 kDa |
| Dosage Form | Sterile lyophilized powder for IV administration |
FDA documentation reports the molecular weight of Gemtuzumab Ozogamicin at approximately 151–153 kDa.
Gemtuzumab Ozogamicin binds to the CD33 antigen expressed on leukemic myeloid cells. Following binding, the antibody-drug conjugate is internalized by the target cell.
Inside the cell, the linker is processed and the calicheamicin derivative is released. Calicheamicin interacts with DNA and produces double-strand DNA breaks, leading to inhibition of DNA synthesis and ultimately cell death.
Gemtuzumab Ozogamicin is used as a targeted antineoplastic agent for CD33-positive acute myeloid leukemia.
The API is relevant to:
The FDA Purple Book identifies Gemtuzumab Ozogamicin as an injectable biological product administered by the intravenous route.
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 2.0% |