Carcinogenic properties of ulipristal acetate (UPA), a selective progesterone receptor modulator developed for
the treatment of benign gynecological conditions such as uterine fibroids, were assessed in a 26-week carcinogenicity
study in transgenic TgRasH2 mice and a 104-week study in Sprague Dawley rats. Dose levels used in the mouse study
were 15, 45, or 130 mg/kg/day and for the ratstudy the doses used were 1, 3, or 10 mg/kg/day. Vehicle and water controls
were part of both studies and a positive control, N-Nitroso-N-methylurea intraperitoneally, was included in the transgenic
mouse assay. Survival at all dose levels was similar to vehicle controls in both sexes of both species and there was no
evidence of any UPA-induced carcinogenicity in either species. Rats receiving UPA had decreased incidences of
fibroadenomas and adenocarcinomas in the mammary gland in all treated groups. UPA exposure [AUC(0–24h)] at the
highest dose in rats was 67 times human therapeutic exposure at 10 mg/day. In mice, no tumor of any type increased at
UPA exposures up to 313 times of therapeutic exposure.
UPA-related findings in mice were limited to organ weight changes in the liver, pituitary, thyroid/parathyroid glands, and
epididymis as well as minimal panlobular hepatocellular hypertrophy in male and female mice receiving 130 mg/kg/day.
Rats had UPA-related non-neoplastic findings in the reproductive system (mammary gland, ovary, uterus, vagina, seminal
vesicle, prostate), endocrine system (adrenal, pituitary), thymus, muscle, liver, pancreas and lungs most of which are
considered to be due to exaggerated pharmacological action of the compound.