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Precedia/Multispecific antibodies/Bizengri/Flexibility

Bizengri: what flexibility did regulators accept, and why?

zenocutuzumab · HER2 x HER3
Check my plan vs. these
Flexibility accepted
DARTAccepted
No reproductive or developmental toxicity studies; literature-based weight-of-evidence assessment of HER2/HER3 inhibition instead
Why: Mechanism-based literature weight of evidence, an alternative approach described in FDA oncology reproductive toxicity guidance · Within the guideline · Weight of evidence · Pharmacology or kinetics
“Rather, the Applicant provided a literature-based weight-of-evidence (WOE) assessment of the potential reproductive toxicity of zenocutuzumab based on its mechanism of action, consistent with the alternative approach described in the FDA Guidance for Industry, Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations.”
✓ VerifiedFDA multi-discipline review, p. 58Source ↗
“FDA agreed that the weight-of-evidence approach for reproductive risk assessment appeared acceptable and sufficient to support the filing of a BLA.”
✓ VerifiedFDA multi-discipline review, p. 48Source ↗

Same question, other multispecifics

Blincyto

blinatumomab · CD19 x CD3
Chimpanzee the only relevant species; limited non-terminal chimpanzee studies plus mouse studies with murine surrogate muS103new

Columvi

glofitamab · CD20 x CD3
No repeat-dose study longer than 4 weeks; 13-week monkey study waived

Elrexfio

elranatamab · BCMA x CD3
No reproductive or developmental toxicity studies; reproductive organs assessed in the 3-month study in sexually mature monkeys

Epkinly

epcoritamab · CD20 x CD3
No 3-month monkey study; exposure could not be maintained with repeated dosing

Hemlibra

emicizumab · FIXa x FX
No carcinogenicity studies for a chronic prophylactic antibody; written carcinogenicity assessment used instead

Imdelltra

tarlatamab · DLL3 x CD3
Monkey 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 CD3
No pharmacologically relevant species; limited single-dose studies plus partially active murine surrogate BiLu

Lunsumio

mosunetuzumab · CD20 x CD3
Monkey embryo-fetal and pre-/postnatal development study waived; weight-of-evidence assessment using other anti-CD20 antibodies

Lynozyfic

linvoseltamab · BCMA x CD3
Planned 26-week monkey study shortened after declining body condition in all dose groups; no 26-week study

Ordspono

odronextamab · CD20 x CD3
No embryo-fetal development study; literature and nonclinical data risk assessment instead

Removab

catumaxomab · EpCAM x CD3
No relevant species: no repeat-dose, genotoxicity, carcinogenicity or reproductive toxicity studies submitted

Rybrevant

amivantamab · EGFR x MET
No embryo-fetal development study; weight-of-evidence assessment of reproductive and embryo-fetal risk instead

Talvey

talquetamab · GPRC5D x CD3
No cross-reactivity of talquetamab with monkey GPRC5D; pivotal monkey toxicology used a surrogate tool molecule (JNJ-64024701)

Tecvayli

teclistamab · BCMA x CD3
Only a 5-week repeat-dose monkey study; no 13-week study

Vabysmo

faricimab · VEGF-A x Ang-2
No 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

Summary across all 18 multispecifics →