Bizengri
zenocutuzumab · HER2 x HER3No reproductive or developmental toxicity studies; literature-based weight-of-evidence assessment of HER2/HER3 inhibition instead
Lynozyfic: what flexibility did regulators accept, and why?
linvoseltamab · BCMA x CD3
Flexibility accepted
Study lengthAcceptedBeyond the letter
Planned 26-week monkey study shortened after declining body condition in all dose groups; no 26-week study
Why: FDA did not request a 26-week study
“A subsequent toxicology study was initially planned as a 26-week repeat-dose study with once weekly dosing at 1, 5, and 20 mg/kg; the FDA did not request the study to be 26 weeks in duration. The study protocol was amended due to the declining body conditions across all dose groups compared to control.”
DARTAcceptedBeyond the letter
No standalone fertility or embryo-fetal studies; fertility endpoints in the 5-week monkey study and weight-of-evidence assessment of developmental risk
Why: In vivo studies of limited value to understand or communicate the risk to patients with advanced cancer · Serious disease
“Standalone fertility studies were not conducted by the applicant as male and female fertility endpoints were evaluated in the 5-week study and specific immunotoxicology endpoints were evaluated in both the 5- and 9- or 14-week studies repeat dose toxicity studies.”
“Based on the above, in vivo studies are deemed not warranted because of the limited value to further understand or communicate the risk to patients with advanced cancer.”
Same question, other multispecifics
Blincyto
blinatumomab · CD19 x CD3Chimpanzee the only relevant species; limited non-terminal chimpanzee studies plus mouse studies with murine surrogate muS103new
Columvi
glofitamab · CD20 x CD3No repeat-dose study longer than 4 weeks; 13-week monkey study waived
Elrexfio
elranatamab · BCMA x CD3No reproductive or developmental toxicity studies; reproductive organs assessed in the 3-month study in sexually mature monkeys
Epkinly
epcoritamab · CD20 x CD3No 3-month monkey study; exposure could not be maintained with repeated dosing
Hemlibra
emicizumab · FIXa x FXNo carcinogenicity studies for a chronic prophylactic antibody; written carcinogenicity assessment used instead
Imdelltra
tarlatamab · DLL3 x CD3Monkey used as the only toxicology species although DLL3 is intracellular in normal tissues, so toxicity may be underrepresented
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)No in vivo toxicology; all toxicology in vitro with human tissues and cells (no relevant species for HLA-restricted TCR and human CD3)
Korjuny
catumaxomab · EpCAM x CD3No pharmacologically relevant species; limited single-dose studies plus partially active murine surrogate BiLu
Lunsumio
mosunetuzumab · CD20 x CD3Monkey embryo-fetal and pre-/postnatal development study waived; weight-of-evidence assessment using other anti-CD20 antibodies
Ordspono
odronextamab · CD20 x CD3No embryo-fetal development study; literature and nonclinical data risk assessment instead
Removab
catumaxomab · EpCAM x CD3No relevant species: no repeat-dose, genotoxicity, carcinogenicity or reproductive toxicity studies submitted
Rybrevant
amivantamab · EGFR x METNo embryo-fetal development study; weight-of-evidence assessment of reproductive and embryo-fetal risk instead
Talvey
talquetamab · GPRC5D x CD3No cross-reactivity of talquetamab with monkey GPRC5D; pivotal monkey toxicology used a surrogate tool molecule (JNJ-64024701)
Tecvayli
teclistamab · BCMA x CD3Only a 5-week repeat-dose monkey study; no 13-week study
Vabysmo
faricimab · VEGF-A x Ang-2No rodent carcinogenicity studies for a chronic ophthalmic product; weight-of-evidence assessment instead
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)No reproductive and developmental toxicity studies; HER2-antibody class weight-of-evidence assessment instead