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.