Antibody-drug conjugate resurgence continues with Lumoxiti

With today’s approval of Astrazeneca’s Lumoxiti the US market has two antibody-drug conjugates against the CD22 antigen. While the first, Pfizer’s Besponsa, was approved a year ago for treating relapsed adult acute lymphoblastic leukaemia (ALL), Astra has positioned Lumoxiti against hairy cell leukaemia, a relatively rare malignancy. Both these haematological cancers affect B cells, hence the relevance of hitting CD22, an antigen present on this cell lineage. An important difference between Besponsa and Lumoxiti is the cytotoxic payload each carries – respectively calicheamicin, the same as that used in Pfizer’s Mylotarg, and Pseudomonas exotoxin A. And both drugs’ labels carry boxed warnings, respectively for liver damage and capillary leak syndrome, the toxicity that briefly derailed Stemline’s anti-CD123 conjugate SL-401. The next anti-CD22 asset to test the regulators could be Immunomedics’ epratuzumab, though as this is a standard “naked” antibody it is unlikely to match the efficacy of more advanced constructs like conjugates and bispecifics. The big competitor could emerge in the form of CD22-directed CAR-T therapy, though this is still some way off being commercialised.

Anti-CD22 antibody-drug conjugates
Project  Pharmacology class  Company  Lead indication  2024e sales ($m)
Besponsa (inotuzumab ozogamicin) Anti-CD22 MAb-calicheamicin conjugate  Pfizer/ UCB   ALL  519
Lumoxiti (moxetumomab pasudotox) Anti-CD22 MAb-PE38  conjugate  Astrazeneca   Hairy cell leukaemia  218
Phase II  
Pinatuzumab vedotin   Anti-CD22 MAb-monomethyl auristatin E conjugate  Roche/ Seattle Genetics  NHL  NA
Phase I  
BAY1862864   Anti-CD22 MAb-thorium 227 conjugate  Immunomedics/ Bayer   NHL  NA
ASCT-602 Anti-CD22 MAb-pyrrolobenzodiazepine conjugate ADC Therapeutics NHL, ALL NA
TRPH-222 Anti-CD22 MAb-4AP drug conjugate Triphase Accelerator/ Celgene NHL NA
ALL=acute lymphoblastic  leukaemia; NHL=non-Hodgkin lymphoma; NA=not available. Source: EvaluatePharma. 

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