Pre-clinical Studies

Eribulin mesilate was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test). Eribulin was positive in the mouse lymphoma mutagenesis assay and was clastogenic in the in vivo rat micronucleus assay.

No carcinogenicity studies have been conducted with eribulin.

A fertility study was not conducted with eribulin, but based on non-clinical findings in repeated-dose studies where testicular toxicity was observed in both rats (hypocellularity of seminiferous epithelium with hypospermia/aspermia) and dogs, male fertility may be compromised by treatment with eribulin. An embryofetal development study in rat confirmed the developmental toxicity and teratogenic potential of eribulin mesilate. Pregnant rats were treated with 0.01, 0.03, 0.1 and 0.15 mg/kg at gestation days 8, 10 and 12. Dose related increased number of resorptions and decreased fetal weight were observed at doses ≥ 0.1 mg/kg and increased incidence of malformations (absence of lower jaw, tongue, stomach and spleen) was recorded at 0.15 mg/kg.