inotuzumab ozogamicin

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Ligands
inotuzumab ozogamicin

GtoPdb Ligand ID: 8266

Synonyms: Besponsa® | CMC-544

inotuzumab ozogamicin is an approved drug (EMA & FDA (2017))

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 [1]. The calicheamicin derivative is N-acetyl gamma calicheamicin dimethylhydrazide as reported by DiJoseph et al (2004) [1].

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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 [2]. 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. In March 2024 FDA approval was expanded to include treatment of relapsed/refractory CD22-positive B-cell precursor ALL in paediatric patients (>1 yr old).

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 [2]. 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.
In March 2024 FDA approval was expanded to include treatment of relapsed/refractory CD22-positive B-cell precursor ALL in paediatric patients (>1 yr old).

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.

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 Trials
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