Elagolix with add-back therapy appears efficacious despite uterine and fibroid factors

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Dr. Ayman Al-Hendy

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.