Date: 2017-01-17
Type of information: Results
phase: 3
Announcement: results
Company: Gedeon Richter (Hungary) Allergan (Ireland)
Product: ulipristal acetate
Action
mechanism: progesterone receptor antagonist. Ulipristal acetate is a selective progesterone receptor modulator, characterised by a tissue-specific partial progesterone antagonist effect. It acts directly on the progesterone receptors in 3 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. In Europe, ulipristal acetate is marketed under the trade name Esmya® by Gedeon Richter, and is currently approved for the pre-operative and intermittent treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. In Canada , ulipristal acetate, available under the trade name Fibristal™, received Health Canada approval in June 2013 for the treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of reproductive age, who are eligible for surgery. To date, more than 300,000 women have been treated with ulipristal acetate for fibroids in over 50 countries.
Disease: uterine fibroids
Therapeutic area: Gynecology - Women's health
Country: Canada, USA
Trial
details: The Venus II study was a multi-center, randomized, 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 6 menstrual cycles, menstrual blood loss =80 mL as measured by the alkaline hematin method over the first 8 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 randomized to ulipristal acetate 5 mg, 10 mg or placebo for two separate 12-week treatment courses followed by a 12-week treatment-free follow-up period.
The Venus I and II trials build upon data collected from prior efficacy and safety studies of ulipristal acetate for fibroids conducted Ex-US. In Europe , ulipristal acetate is marketed under the trade name Esmya® by Gedeon Richter.
Latest
news: * On January 17, 2017, Allergan and Gedeon Richter announced 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.
The study included 432 U.S. patients with 162 and 157 patients randomized to ulipristal acetate 5 and 10 mg respectively, and 113 to placebo. The average age of patients enrolled was 41 years and 67 percent 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 10 mg group (54.8%) and the 5 mg group (42.0%) 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.
More patients in the 10 mg group (55.4%) and the 5 mg group (34.6%) achieved absence of bleeding within 10 days after treatment initiation in Treatment Course One compared to placebo (0.0%). Significantly more patients in the 10 mg group (57.3%) and the 5 mg group (40.5%) achieved absence of bleeding compared to placebo (8.0%) in Treatment Course Two. The improvement from baseline in the UFS-QOL revised activities subscale was significantly greater in the 10 mg group (56.7%) and the 5 mg group (48.3%) compared to placebo (13.0%).
The UFS-QOL is a validated fibroid-specific symptom and health-related quality of life instrument. This questionnaire is an established instrument to assess disease impact on the well-being of women with uterine fibroids.
The most common adverse events (=5%) on ulipristal acetate treatment were hot flush, headache, fatigue, and nausea in the combined period of Treatment Course One and first off-treatment interval. The most common adverse event (= 5%) on ulipristal acetate treatment was headache in the combined period of Treatment Course Two and second off-treatment interval.
