AbbVie presented data from two Phase 2 clinical trials showing that elagolix, with or without add-back therapy, led to a rapid reduction of heavy menstrual bleeding compared to a placebo in women with uterine fibroids. Uninterrupted treatment also was associated with decreased symptom severity and improved quality of life.
The data were recently presented at the American Society for Reproductive Medicine Scientific Congress & Expo (ASRM) in San Antonio, Texas.
Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist, meaning it blocks GnRH signaling by binding to GnRH receptors in the pituitary gland. Administered orally, it inhibits the secretion of hormones — luteinizing hormone (LH) and follicle-stimulating hormone (FSH) — which in turn halts the production of estrogen in the ovaries. Elagolix inhibition is reversible and dose-dependent, so that hormone secretion is resumed once the therapy is removed.
In the study, “Elagolix treatment in women with heavy menstrual bleeding-associated with uterine fibroids: efficacy and safety results from a Phase 2b study,” researchers evaluated elagolix with and without add-back therapy in premenopausal women with heavy menstrual bleeding associated with uterine fibroids.
The Phase 2b study (NCT01817530) recruited women who were randomized into two groups. The first group received 300 mg of elagolix administered twice daily, and the second group received 600 mg of elagolix once daily.
Elagolix was administered either alone or combined with add-back therapy (estradiol/norethindrone acetate). The effects of elagolix, either administered alone or in combo, were evaluated against a placebo group of women with uterine fibroids.
The add-back therapy was administered in two doses: a low dose of 0.5 mg estradiol/0.1 mg norethindrone acetate and a standard dose of 1.0 mg estradiol/0.5 mg norethindrone acetate. The treatment was given for six months.
The study’s primary goal was to assess changes in menstrual blood loss measured by the alkaline hematin method, a standard measurement for menstrual blood loss (MBL). Specifically, researchers looked at the percentage of women during the last 28 days of treatment with no more than 80 mL MBL and at least a 50% reduction in MBL from the start of the study through the sixth month.
The trial’s secondary goals included assessing endometrial health by tissue biopsy and transvaginal ultrasound and changes in bone mineral density (BMD).
Of 259 women enrolled in the first group (elagolix 300 mg), 80% completed treatment. A reduction in menstrual blood loss was achieved in 92% of the women treated with elagolix alone. This clearly contrasts with the 27% of participants in the placebo group who saw a reduction. The combination of elagolix plus low-dose add-back therapy led to a reduction of MBL in 85% of the women, while a standard dose of add-back therapy resulted in an MBL reduction in 79% of them.
Add-back therapy addressed the effects of low estrogen, including hot flushes and a decrease in bone mineral density, seen in the women who received elagolix alone.
All of the groups had a decrease in endometrial thickness, and by the sixth month, elagolix-treated groups had normal quiescent/minimally stimulated endometrium.
Effectiveness and safety outcomes were similar in patients randomized to the second group (elagolix 600 mg).
Overall, “elagolix with or without add-back significantly reduced MBL in UF [uterine fibroids]-associated HMB [heavy menstrual bleeding]. Add-back therapy attenuated the hypoestrogenic [low levels of estrogen] effects of elagolix. There were no adverse endometrial findings,” the researchers concluded.
In a second presentation, “Elagolix improves quality of life in women with heavy menstrual bleeding associated with uterine fibroids: evidence from a phase 2b randomized trial,” researchers evaluated the effects of elagolix on the health-related quality of life (HRQL) in women with heavy menstrual bleeding associated with uterine fibroids.
Participants again were randomized into two main groups receiving 300 mg and 600 mg of elagolix. Each group was then divided into four subgroups receiving a placebo, elagolix alone, or elagolix plus add-back therapies of estradiol/norethindrone acetate in low and standard doses.
Researchers assessed changes in health-related quality of life at the start of the study and at months 1, 3, and 6 of treatment using the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire.
Uninterrupted treatment with elagolix (both at 300 mg and 600 mg) led to improvements in health-related quality of life, including activities, energy, mood, control, and self-consciousness, and lowered symptom severity when compared to a placebo. In the 300 mg elagolix group, participants also experienced a statistically significant improvement in sexual function.
These results show that “elagolix with and without hormonal add-back therapy improved symptom severity and HRQL among women with HMB associated with UF,” researchers said.
AbbVie has an ongoing Phase 3 elagolix uterine fibroids program that includes a replicate six-month study to look at elagolix’s effectiveness and safety (NCT02691494), followed by a six-month safety and effectiveness extension study (NCT02925494).