Bizengri
zenocutuzumab · HER2 x HER3Mouse xenografts: HER2+ breast cancer (JIMT-1) and NRG1 fusion-positive lung and pancreatic patient-derived xenografts
Hemlibra: animal efficacy model or human cells?
emicizumab · FIXa x FX
Efficacy evidence
Cynomolgus monkey models of acute and chronic hemophilia A
“The in vivo pharmacological effects of emicizumab were assessed in cynomolgus monkey models of acute and chronic hemophilia A as described below.”
Why that model
Emicizumab cross-reacts only with monkey (not rat or mouse) FIXa/FX, so hemophilia was induced in monkeys
“In an enzyme assay using purified Cynomolgus monkey, rat and mouse FIXa and FX, emicizumab was found to cross-react only with the corresponding clotting factors of Cynomolgus monkeys.”
Reviewer's view of the efficacy data
EMA: monkey hemophilia models supportive though initially poorly characterised; parameter choice later justified
“While the results are supportive of the proposed use, at the time of initial application, the models were poorly characterised. However, adequate justification of the choice of parameters measured was subsequently provided.”
Same question, other bispecifics
Blincyto
blinatumomab · CD19 x CD3Blinatumomab in NOD/SCID mouse tumor xenograft models
Columvi
glofitamab · CD20 x CD3Human HSC-engrafted NOG/NSG mice, non-tumor-bearing and tumor-bearing
Elrexfio
elranatamab · BCMA x CD3Multiple myeloma xenograft models (MM.1S, OPM2, MOLP8) with varying BCMA expression
Epkinly
epcoritamab · CD20 x CD3Human lymphoma cell line-derived xenograft (CDX) mouse models and one patient-derived xenograft (PDX) model
Imdelltra
tarlatamab · DLL3 x CD3Xenograft models in NSG mice injected with activated, expanded human T cells
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Mice engrafted with HLA-A*02:01/gp100+ Mel526 human melanoma cells plus human PBMCs; tumor growth inhibition
Korjuny
catumaxomab · EpCAM x CD3SCID mouse i.p. human ovarian carcinoma ascites xenograft treated with human PBMCs plus catumaxomab
Lunsumio
mosunetuzumab · CD20 x CD3Human CD20/CD3 double-transgenic mice: peripheral and tissue B-cell depletion and T-cell activation (comparable to analogue 2H7v16/40G5c)
Lynozyfic
linvoseltamab · BCMA x CD3NSG mice co-implanted with human PBMC and NCI-H929 or MOLP-8 myeloma xenografts
Ordspono
odronextamab · CD20 x CD3Lymphoma tumour models in humanized (BRG) mice and immunodeficient NSG mice
Removab
catumaxomab · EpCAM x CD3Human ovarian carcinoma xenograft (catumaxomab); syngeneic human-EpCAM mouse tumour model with surrogate BiLu
Rybrevant
amivantamab · EGFR x METPatient-derived tumor xenografts with EGFR exon 20 insertion mutations in mice
Talvey
talquetamab · GPRC5D x CD3Myeloma cell line xenografts (H929 prophylactic; MM.1S, RPMI 8226 established) in humanized immunodeficient mice
Tecvayli
teclistamab · BCMA x CD3Human MM xenografts (H929, RPMI-8226) in human PBMC/T-cell-engrafted NSG mice
Vabysmo
faricimab · VEGF-A x Ang-2Laser-induced choroidal neovascularization (nAMD model) in cynomolgus monkeys, IVT faricimab vs ranibizumab
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)HER2 3+ xenografts in nude mice (SKOV-3, NCI-N87, patient-derived GXA 3054); no effect in HER2-negative model