Phase 3 Study Finds Elagolix Plus Hormone Therapy Combats Heavy Menstrual Bleeding in Uterine Fibroid Patients

Phase 3 Study Finds Elagolix Plus Hormone Therapy Combats Heavy Menstrual Bleeding in Uterine Fibroid Patients

Results from the Phase 3 ELARIS UF-EXTEND trial show that treatment for a year with elagolix combined with low-dose hormone therapy led to a significant decrease in heavy menstrual bleeding in 87.9 percent of women with uterine fibroids, AbbVie and Neurocrine Biosciences, the medication’s developers, announced.

Elagolix was approved in late July in the United States for the treatment of endometriosis pain, under the name Orilissa.

The extension study is part of the Elagolix Phase 3 Uterine Fibroids Program, which included two prior Phase 3 trials, ELARIS UF-I (NCT02654054) and ELARIS UF-II (NCT02691494). These evaluated the effectiveness and safety of elagolix alone (300 mg twice daily) or in combination with low-dose sex hormone therapy (estradiol 1.0 mg/norethindrone acetate 0.5 mg), compared to a placebo in women with uterine fibroids for six months.

Each trial enrolled about 400 premenopausal women (ages 18–51) with uterine fibroids. Previous data showed that 68.5 percent and 76.2 percent of women, in ELARIS UF-I and UF-II respectively, who received elagolix as an add-on therapy for six months achieved clinical response, defined as a 50% or greater reduction in menstrual bleeding over the course of the six-month study, and a loss of less than 80 mL of blood during month six.

The ELARIS UF-EXTEND study (NCT02925494) evaluated the long-term efficacy and safety of elagolix administered alone and in combination with low-dose sex hormone therapy in women who had already received six months of treatment in the ELARIS UF-I and UF-II trials.

Women were treated for a total of 12 months. Participants continued to receive either 300 mg of elagolix twice daily or 300 mg of elagolix twice daily in combination with hormone therapy. Those who had been randomized to a placebo in the previous studies were randomized to elagolix alone or the combo therapy.

The study’s primary endpoint was to assess the percentage of women who achieved at least a 50% reduction in menstrual bleeding, measured by the alkaline haematin method that estimates the blood concentration of hemoglobin — the protein that carries oxygen throughout the body.

Along with a significant reduction in heavy menstrual bleeding, the results of the combo therapy were consistent with previous trials. The most frequent adverse events included hot flashes, night sweats, nausea, headache and nasopharyngitis.

After 12 months, the decrease in bone mineral density was lower in women treated with the combo therapy compared to women who received elagolix alone.

All the data will support regulatory submission for elagolix in uterine fibroids, expected in 2019.

Endometriosis and uterine fibroids present similar symptoms, such as menstrual irregularity and pelvic pain. Uterine fibroids are noncancerous tumors that cause heavy menstrual bleeding.

Elagolix blocks the receptor of the gonadotropin-releasing hormone (GnRH). By blocking the receptors of GnRH, elagolix lowers levels of the sex hormones estrogen and progesterone, which are linked to the development and worsening of endometriosis and uterine fibroids.

“Women with uterine fibroids are in need of additional medical management options that could help address unresolved symptoms,” Dawn Carlson, MD, master of public health and vice president, general medicine development for AbbVie, said in a press release.

“The results from this extension study provide additional information on the use of elagolix for up to 12 months in the management of heavy menstrual bleeding associated with uterine fibroids,” Carlson said.