Allergan Plc and Gedeon Richter Plc. 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.

"We are pleased with the favorable results of Venus II supporting the efficacy and safety profile of ulipristal acetate as shown in our Venus I trial," said David Nicholson, chief research and development officer, Allergan. "Allergan is committed to identifying, developing and bringing to market therapies that address unmet need and provide significant value to the healthcare system, including a potential new treatment for symptomatic uterine fibroids.  We are confident that the results of our phase III trials for ulipristal acetate may potentially offer the first and only oral treatment option for women suffering from uterine fibroids in the US."

The study included 432 US 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 per cent 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.

"It is indeed very encouraging that we have another successful phase III study conducted in patients with uterine fibroid symptoms, which shows that ulipristal acetate could bring promising treatment for women suffering from this condition," added Dr István Greiner, research director of Gedeon Richter Plc. "We remain committed to the development of female healthcare products aiming towards the improvement of the quality of life of women in all age groups."

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.

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.

Ulipristal acetate, an investigational drug for the medical treatment of uterine fibroids, is a selective progesterone receptor modulator (SPRM), which 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. 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.

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. In Canada, ulipristal acetate is available under the trade name Fibristal. Esmya and Fibristal are currently approved for the pre-operative and intermittent treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age.

To date, more than 310,000 women have been treated with ulipristal acetate for fibroids in over 65 countries worldwide.

Uterine fibroids, also known as myomas, are the most common benign growths that affect up to 80 percent of women in the United States by the age of 50 and are more prevalent in African-American women. Fibroids are made of muscle cells and other tissues that grow in and around the wall of the uterus, or womb. Uterine fibroids are a significant cause of morbidity. It is estimated that up to 50 percent of women with fibroids will experience symptoms. Women report serious symptoms such as heavy menstrual bleeding, painful menses, pelvic pain, urinary symptoms, bowel dysfunction, pressure within the abdomen and on adjacent pelvic organs, and impact on fertility. In fact, women reported severe to very severe symptoms related to menstrual pain/cramps, heavy or prolonged bleeding, and abdominal pain/cramping. Moreover, heavy uterine bleeding can be associated with iron deficiency anemia, pain, social embarrassment, interference with daily and social activities as well as lost productivity in the work place.

The current mainstay of management is mainly surgical. In fact, uterine fibroids are responsible for over 350,000 hospitalizations and are the leading cause of hysterectomies, accounting for approximately one-third of all hysterectomies annually in the US. The economic burden of uterine fibroids is also large, costing the economy over $34 billion each year.

Allergan plc is a bold, global pharmaceutical company and a leader in a new industry model – Growth Pharma.  Allergan is focused on developing, manufacturing and commercializing branded pharmaceuticals, devices and biologic products for patients around the world.

Gedeon Richter Plc. headquartered in Budapest/Hungary, is a major pharmaceutical company in Central Eastern Europe, with an expanding direct presence in Western Europe. Having reached a market capitalisation of EUR 3.3 billion (US$ 3.6 billion) by the end of 2015, Richter's consolidated sales were approximately EUR 1.2 billion (US$ 1.3 billion) during the same year.