Date: 2016-05-09
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:
Trial
details: Venus I study is a multi-center, randomized, double-blind, placebo-controlled clinical trial in premenopausal women 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 1:1:1 to ulipristal acetate 5 mg, 10 mg or placebo for one 12-week treatment course followed by a 12- week treatment-free follow-up period. African-American women represented 69% of patients enrolled. The average BMI was 31.7.
The Venus I trial, is the first completed pivotal study of ulipristal acetate for uterine fibroids in the US population. It is designed to meet FDA requirements for approval.
Latest
news: * On May. 9, 2016, Allergan and Gedeon Richter announced positive results from Venus I, one of two pivotal Phase III clinical trials evaluating the efficacy and safety of ulipristal acetate in women with uterine fibroids. The study included 157 patients, with 101 patients randomized to ulipristal acetate 5 and 10 mg and 56 to placebo. 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. Significantly more patients in the 10 mg group (58.3%; p<0.0001) and the 5 mg group (47.2%; p<0.0001) achieved absence of bleeding compared to placebo (1.8%).
The secondary efficacy endpoints were the percentage of patients with absence of uterine bleeding from Day 11 to end of treatment and the change from baseline in the UFS-QOL revised Activities subscale at the end of treatment. Significantly more patients in the 10 mg group (58.3%; p<0.0001) and the 5 mg group (43.4%; p<0.0001) achieved absence of bleeding from Day 11 to the end of treatment compared to placebo (0%). The improvement from baseline in the UFS-QOL revised Activities subscale was significantly greater in the 10 mg group (59.0; p<0.0001) and the 5 mg group (52.1; p<0.0001) compared to placebo (21.2).
The UFS-QOL is a disease-specific symptom and health-related quality of life questionnaire. This questionnaire is an established instrument to assess disease impact on patient's well-being in women with uterine fibroids.
There were no treatment-related serious adverse events. No patients discontinued ulipristal acetate treatment due to adverse events. The most common adverse events (= 5%) on ulipristal acetate treatment were hypertension (N=6), blood creatine phosphokinase increased (N=5), hot flush (N=5), and acne (N=3).
Venus I is the first clinical trial to report topline results. The second of two clinical trials--Venus II--is anticipated to be completed this year with topline results expected in the first half of 2017. A new drug application for the treatment of uterine fibroids is planned to be submitted in 2017.
