Ulipristal acetate: in uterine fibroids.

Ulipristal acetate, a selective progesterone-receptor modulator, inhibits the proliferation and induces apoptosis of leiomyoma cells in vitro. It also modulates the expression of vascular endothelial growth factors and hormone receptors and modulates extracellular matrix breakdown in leiomyoma cells but not in myometrial cells. In two randomized, double-blind, multinational phase III trials of 13 weeks' duration in women aged 18-50 years with uterine fibroids, a once-daily regimen of oral ulipristal acetate 5 mg/day controlled excessive uterine bleeding (primary endpoint) in ≥90% of patients. Ulipristal acetate 5 mg/day was more effective than placebo and was shown to be noninferior to intramuscular leuprolide acetate 3.75 mg once monthly in controlling uterine bleeding. Uterine bleeding was rapidly controlled by ulipristal acetate. Approximately half of recipients of ulipristal acetate 5 mg/day became amenorrhoeic within the first 10 days of treatment. Furthermore, uterine bleeding was controlled significantly more rapidly for recipients of ulipristal acetate than recipients of leuprolide acetate. A significantly greater median reduction from baseline in total fibroid volume was observed for recipients of ulipristal acetate 5 mg once daily than recipients of placebo following 13 weeks' treatment (coprimary endpoint). For patients who did not undergo surgery, the volume reduction was maintained for at least 6 months after discontinuing treatment. Ulipristal acetate was generally well tolerated in women with uterine fibroids. The incidence of hot flush occurred with a significantly lower frequency for recipients of ulipristal acetate than for recipients of leuprolide acetate.