New Medication Gets FDA Approval for Fibroid-Associated Menstrual Bleeding

Oriahnn, a capsule that contains elagolix, estradiol and norethindrone acetate, has received approval from the US Food and Drug Administration (FDA) for management of heavy menstrual bleeding in premenopausal women with uterine leiomyomas (fibroids). Elagolix is an oral, nonpeptide gonadotropin-releasing hormone (GnRH) antagonist that suppresses ovarian sex hormones. It works quickly, suppressing hormones within 24 hours of treatment initiation, and, with a short half-life, can be easily reversed. Combining it with the hormones is designed to mitigate associated hypoestrogenic side effects.

“With longer waits for non-emergency procedures during the COVID-19 pandemic, such as surgery for fibroids, it’s great that women will soon have a new oral treatment for fibroid-related bleeding,” says Cleveland Clinic’s Linda Bradley, MD, Professor of Ob/Gyn and Reproductive Biology, Medical Director of the American Association of Gynecologic Laparoscopists (AAGL) and an author on the studies of elagolix and Oriahnn.

When Oriahnn will be commercially available and what it will cost are still to be determined. Other treatment options for uterine fibroids include various means of birth control, tranexamic acid (Lysteda), myomectomy, uterine fibroid embolization (UFE) and hysterectomy.

The burden of heavy bleeding

Uterine fibroids are clinically apparent in approximately 25% of women, but may be present and asymptomatic in closer to 70% of women. Notably, the incidence of uterine fibroids is two to three times higher among black women than among white women. The primary symptom of uterine fibroids is heavy menstrual bleeding. Additional symptoms include pelvic pain and pressure, urinary or gastrointestinal issues (such as frequency and difficult emptying or constipation) and infertility. Uterine fibroids account for 30% of hysterectomies in white women and more than 50% of hysterectomies in black women.

“Uterine fibroids can significantly alter a patient’s quality of life, causing pain and bulk symptoms that affect everything from sexual health to social well-being. Additionally, fibroids can change a woman’s perception of herself and her body, and heavy bleeding can be a cause of social embarrassment. This is a condition that impacts relationships, employment and overall physical and mental health,” Dr. Bradley explains.

Drug reduces bleeding in premenopausal patients

Approval of the combination pill was based on the results of included two randomized, placebo-controlled, six-month trials of elagolix. Combined, nearly 800 premenopausal women whose uterine fibroids had been confirmed by ultrasonography received 300 mg of elagolix twice daily with or without hormonal add-back therapy (1 mg of estradiol and 0.5 mg of norethindrone acetate, once daily) or a placebo. The primary end points were a reduction in menstrual blood loss of at least 50% from baseline and menstrual blood loss of less than 80 ml during the final treatment month.

Women receiving elagolix were much more likely to achieve the primary end points. In one trial (UF-1), 84.1% of women taking elagolix alone and 68.5% of women taking elagolix with add-back therapy met the primary end points, compared with 8.7% in the placebo group. In the other trial (UF-2), 77% of women taking elagolix alone and 76.5% receiving elagolix with add-back therapy met the primary end points, compared with 10% in the placebo group. Add-back hormonal therapy attenuated elagolix-related menopausal symptoms, including hot flushes and decreases in mineral bone density.

Women with uterine fibroids feel better on elagolix

Improvements were also noted in several secondary end points among women randomized to an elagolix regimen, including:

• A greater reduction in menstrual blood loss.
• A greater percentage of women whose hemoglobin levels increased more than 2 g per deciliter (from a baseline level of 10.5 g per deciliter or less).
• Significant improvements in scores on the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire.

“Importantly, women taking elagolix no longer felt that their bleeding was significant. Patients also feel better as their hemoglobin increases, which we observed with elagolix. They report less pain, feel more energetic and their pallor improves,” Dr. Bradley says.

Trial recruitment mirrors patient population

The study is notable for its racial inclusiveness, according to Dr. Bradley, who also serves as Vice Chair for Diversity and Inclusion of the Ob/Gyn & Women’s Health Institute at Cleveland Clinic.

Racial composition of trial participants — no./total no. (%)

“What makes me proudest [about these trials] was that approximately 68% of the patients that were enrolled of the African diaspora,” says Dr. Bradley. “They have the greatest burden of disease — more and larger fibroids. Their fibroids develop at earlier ages, and all measures of quality of life are worse. I can’t overstate the importance of trial recruitment that truly reflects diversity and inclusion, particularly with what’s happening in our country today.”