Ulipristal acetate is the first oral therapy to demonstrate efficacy and safety for uterine fibroids in two US pivotal studies, a press release states.
Allergan and Gedeon Richter announced positive results from Venus II, the second of two pivotal phase III clinical trials evaluating the efficacy and safety of ulipristal acetate in women with abnormal bleeding due to uterine fibroids. A new drug application filing for ulipristal acetate is planned for the second half of 2017.
Venus II was a multicentre, randomised, double-blind, placebo-controlled clinical trial in premenopausal women in North America between 18 and 50 years old with cyclic (22 to 35 days) abnormal uterine bleeding in ≥4 of the last six menstrual cycles, menstrual blood loss ≥80 mL as measured by the alkaline hematin method over the first eight days of menses, ≥1 discrete uterine fibroid of any size and location observable by transvaginal ultrasound, follicle-stimulating hormone ≤20 mIU/mL, and uterine volume ≤20 weeks by exam. Eligible patients were randomised to ulipristal acetate 5mg, 10mg or placebo for two separate 12-week treatment courses followed by a 12-week treatment-free follow-up period.
The study included 432 patients with 162 patients randomised to ulipristal acetate 5mg, 157 patients to receive 10mg, and 113 patients to placebo. The average age of patients enrolled was 41 years and 67% of enrolled patients were Black/African Americans. The study met all the co-primary and secondary endpoints with both ulipristal treatment arms achieving statistically significant results over placebo (p<0.0001). The co-primary efficacy endpoints were percentage of patients with absence of uterine bleeding and time to absence of uterine bleeding on treatment during Treatment Course One (12-week duration). Significantly more patients in the 10mg group (54.8%) and the 5mg group (42%) achieved absence of bleeding compared to placebo (0%).
The secondary efficacy endpoints were the percentage of patients with absence of uterine bleeding from day 11 to end of the first treatment course; the percentage of patients with absence of uterine bleeding after the second treatment course; time to absence of uterine bleeding on treatment during treatment course two; and the change from baseline in the UFS-QOL revised Activities subscale at the end of the first treatment course. The UFS-QOL is a validated fibroid-specific symptom and health-related quality of life questionnaire.
More patients in the 10mg group (55.4%) and the 5mg group (34.6%) achieved absence of bleeding within 10 days after treatment initiation in the first course of treatment compared to placebo (0%). Significantly more patients in the 10mg group (57.3%) and the 5mg group (40.5%) achieved absence of bleeding compared to placebo (8%) in the second course of treatment. The improvement from baseline in the UFS-QOL revised activities subscale was significantly greater in the 10mg group (56.7%) and the 5mg group (48.3%) compared to placebo (13%).
The most common adverse events (≥5%) on ulipristal acetate treatment were hot flush, headache, fatigue, and nausea in the combined period of first course of treatment and first off-treatment interval. The most common adverse event (≥ 5%) on ulipristal acetate treatment was headache in the combined period of the second course of treatment and second off-treatment interval.
Ulipristal acetate is an investigational drug for the medical treatment of uterine fibroids. It is a selective progesterone receptor modulator (SPRM), which acts directly on the progesterone receptors in three target tissues: the endometrium (uterine lining), uterine fibroids, and the pituitary gland. Ulipristal acetate exerts a direct effect on the endometrium (suppressing uterine bleeding) and direct action on fibroid size by decreasing the formation of new fibroid cells and promoting fibroid cell death. The safety and efficacy of ulipristal acetate has been evaluated in two phase III US studies of more than 589 adult women of reproductive age. Ulipristal acetate is protected by a patent that expires in 2029. To date, more than 310,000 women have been treated with ulipristal acetate for fibroids in over 65 countries worldwide.