- Guide to PHARMACOLOGY
Synonyms: Besponsa® | CMC-544
inotuzumab ozogamicin is an approved drug (EMA & FDA (2017))
Compound class: Antibody
Comment: Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) that targets delivery of the highly cytotoxic ozogamicin (a derivative of calicheamicin γ1) to CD22 (SIGLEC-2) +ve myeloid cells . The calicheamicin derivative is N-acetyl gamma calicheamicin dimethylhydrazide as reported by DiJoseph et al (2004) .
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|The EMA has granted inotuzumab ozogamicin orphan designation for the treatment of the rare disease B-cell acute lymphoblastic leukemia (ALL).
Although Phase 3 clinical trials assessing inotuzumab ozogamicin as a treatment for non-Hodgkin lymphoma have been terminated (NCT01232556 and NCT00562965) because they were unlikely to meet their primary objective of improving overall survival (OS), a separate Phase 3 trial in patients with ALL is ongoing (NCT01564784). Preliminary results from this ALL trial indicated extended progression-free and overall survival with inotuzumab ozogamicin compared to standard therapy . The FDA granted breakthrough therapy designation for inotuzumab ozogamicin for ALL based on these results. The EMA had granted orphan designation for ALL in 2013. Both the EMA and FDA converted to full approval as a treatment for ALL in 2017. Veno-occlusive liver disease was observed as a major adverse event associated with inotuzumab ozogamicin therapy.
|Mechanism Of Action and Pharmacodynamic Effects|
|Calicheamicin γ1 damages DNA by causing strand breaks, this ultimately leads to cell death. Antibody targeting of this cytotoxic agent to specific cells limits bystander damage.|
|Clinical Trial ID||Title||Type||Source||Comment||References|
|NCT00562965||Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)||Phase 3 Interventional||Pfizer|
|NCT01232556||A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy||Phase 3 Interventional||Pfizer|
|NCT01564784||A Study Of Inotuzumab Ozogamicin Versus Investigator's Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia||Phase 3 Interventional||Pfizer|
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)
European Medicines Agency (EMA)