Irish drugmaker Allergan has posted a full house of met endpoints in a late-stage benign uterine tumors trial using a form of the drugmaker’s contraceptive pill Ella.
Allergan and London-based research partner Gedeon Richter have announced positive results from Venus I--one of two pivotal Phase III trials looking at the efficacy and safety of ulipristal acetate in women with uterine fibroids--a type of benign tumor found in the womb, and the leading course of hysterectomies in the U.S.
Ulipristal acetate has something of a long history, having originally been developed and marketed as Esmya for certain patients with uterine fibroids since 2012 in Europe--where it is sold by Gedeon Richter--who a year later received approval for the drug in Canada, but has had no luck in getting it out in the U.S.
Its active ingredient is also marketed by Allergan as the contraception pill Ella in the U.S.
Analysts at EP Vantage note that Allergan--then Watson--had originally sought a license for Esyma with the FDA back in 2013, but a Phase III study in anemia associated with the growths, announced in 2012, was quietly withdrawn before it started enrollment, the firm said.
Its latest study is not, however, measuring change in hemoglobin levels as this trial was, but rather bleeding and time to absence of bleeding, as well as to whether it improves quality of life (its secondary endpoints).
In data released today, the study--which included 157 patients, with 101 patients randomized to ulipristal acetate 5 mg and 10 mg and 56 to placebo--met all the co-primary and secondary endpoints with both ulipristal treatment arms achieving statistically significant results over placebo in reducing bleeding and improving quality of life.
The co-primary efficacy endpoints were percentage of patients with absence of uterine bleeding and time to absence of uterine bleeding--with significantly more patients in the 10 mg group (58.3%) and the 5 mg group (47.2%) achieving an 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.
The UFS-QOL is a disease-specific symptom and health-related quality of life questionnaire. This questionnaire is used to assess disease impact on patient's well-being in women with uterine fibroids.
Significantly more patients in the 10 mg group (58.3%) and the 5 mg group (43.4%) 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%) and the 5 mg group (52.1%) compared to placebo (21.2%).
Umer Raffat, a senior analyst at Evercore ISI, said in a note to clients: “This drug is already approved in Europe and Canada. However, the indication is limited: pre-operative treatment only. On the other hand, FDA is allowing Allergan to enroll patients with signs and symptoms but not necessarily preparing for surgery. This greatly expands the target population for Esmya.
“Having said that, keep in mind Esmya is NOT a chronic therapy. FDA is allowing Esmya to be dosed for one cycle, then break, and then another cycle. Based on the second Phase III trial, perhaps FDA may limit max number of cycles to 2.”
The current market leader--AbbVie's ($ABBV) gonadotropin-releasing hormone analogue Lupron--is usually used for a short period of time because of menopause-like side effects.
Venus I is the first clinical trial to report topline results. The second of two clinical trials, Venus II, is set to be completed this year, according to Allergan, with topline results expected in the first half of 2017. This trial is looking at Esmya as well as intermittent treatment. Should all go well, a new drug application is planned to be submitted next year.
Ulipristal acetate works as a selective progesterone receptor modulator, which acts directly on the progesterone receptors in three target tissues: the uterine lining, uterine fibroids and the pituitary gland.
It 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.
Should it gain FDA approval, the drug is set to become the biggest-selling uterine fibroid drug--with 2020 sales of $519 million, according to Evaluate Pharma consensus forecasts--made up of $352 million in the U.S. and Canada, and $167 million in other territories. Allergan has perhaps unsurprisingly been more bullish, estimating sales of $500 million to $1 billion, and has a patent until 2029.
Allergan recently set out its path of independence after a potential acquisition from Pfizer ($PFE) fell through, with drugs such as this part of a stable of new meds/licenses it will need to hit its sales targets.
- check out the release