What Is Elagolix?
Elagolix, as part of the medication ORIAHNN, is an FDA-approved medication for heavy menstrual bleeding associated with uterine fibroids. It is also approved for the management of moderate to severe pain associated with endometriosis.
Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist. It works by blocking GnRH receptors in the pituitary gland, which reduces the production of hormones like luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This leads to a decrease in estrogen and progesterone levels, which can help manage hormone-dependent conditions.
Beyond its approved uses, Elagolix is currently being investigated in clinical trials for several related conditions. These include uterine fibroids, heavy menstrual bleeding, infertility, and heavy uterine bleeding. Other areas of study include folliculogenesis, aging, fibroid uterus, and menopause. A total of 33 trials have studied Elagolix, with 4 currently recruiting participants.
Uses and Conditions Under Study
Elagolix is primarily studied for conditions related to women's reproductive health, particularly those influenced by hormones.
Endometriosis: This painful disorder affects women of childbearing age, where tissue similar to the lining of the uterus grows outside the uterus. Elagolix, by reducing estrogen levels, aims to alleviate the pain and symptoms associated with this condition. A significant number of trials, 19 in total (17 for Endometriosis and 2 for Endometriosis, Pain), have investigated Elagolix for this use.
Uterine Fibroids and Bleeding: Uterine fibroids are common benign growths in the uterus that can cause symptoms like pelvic pressure and heavy menstrual bleeding. Elagolix is being studied to manage these symptoms, especially heavy menstrual bleeding, by reducing hormone levels that contribute to fibroid growth and excessive bleeding. There are 15 trials focusing on uterine fibroids (7 for Uterine Fibroids, 1 for Fibroid Uterus) and related bleeding (5 for Heavy Menstrual Bleeding, 2 for Heavy Uterine Bleeding).
Infertility and Reproductive Processes: Given its impact on hormone levels, Elagolix is also being explored for its potential role in infertility and other reproductive processes. Some research suggests that conditions like endometriosis can affect IVF outcomes. Elagolix is being studied in 3 trials for infertility, and single trials for folliculogenesis, menopause, and aging.
Dosing
Elagolix is typically administered orally as a tablet. The specific dosage and frequency depend on the condition being treated and whether it is used alone or in combination with other medications.
For approved indications, common dosages include 150 mg once daily or 200 mg twice daily. For instance, one study administered Elagolix at 150 mg once daily. Another trial mentioned 200 mg tablets administered orally BID.
In clinical trials, a wide range of Elagolix strengths and dosing regimens have been investigated, often as part of different cohorts or treatment arms. These include:
- Single-agent Elagolix: Strengths from 25 mg BID to 600 mg QD have been studied. Specific dosages include 50 mg QD, 75 mg BID, 100 mg BID, 250 mg, 300 mg QD, 300 mg BID, and 400 mg QD.
- Elagolix in combination: Elagolix has also been studied alongside estradiol (E2) and norethindrone acetate (NETA), often referred to as "add-back" therapy. These combinations include various Elagolix strengths, such as 300 mg BID or 600 mg QD, with different doses of E2/NETA.
These varied dosages reflect ongoing research to determine the most effective and well-tolerated treatment approaches for different conditions.
Side Effects
The most common side effect reported in clinical trials for Elagolix was hot flush, experienced by 15.3% of patients taking Elagolix, compared to 8.9% on placebo. Headache was reported by 8.3% of patients on Elagolix versus 7.0% on placebo. Nausea occurred in 7.9% of patients taking Elagolix, compared to 7.7% on placebo. Night sweats affected 4.9% of patients on Elagolix, while 2.9% on placebo reported this. Sinusitis was seen in 4.6% of patients taking Elagolix and 4.4% on placebo.
Some side effects were less common in patients taking Elagolix compared to placebo. For example, urinary tract infection affected 4.5% of patients on Elagolix, compared to 5.4% on placebo. Nasopharyngitis (common cold) was reported by 3.9% of patients on Elagolix versus 3.4% on placebo. Insomnia occurred in 3.7% of patients taking Elagolix, compared to 2.6% on placebo. Upper respiratory tract infection was also slightly less common, affecting 3.7% of patients on Elagolix compared to 3.8% on placebo.
Clinical Trial Results
Elagolix for Endometriosis
Clinical trials investigated Elagolix for the management of endometriosis-associated pain. In a study comparing Elagolix to subcutaneous depot medroxyprogesterone acetate (DMPA-SC) (NCT00437658), 86.0% of patients receiving Elagolix 150 mg once daily experienced a response in dysmenorrhea (menstrual pain), similar to the 86.3% on DMPA-SC. Elagolix 150 mg once daily also showed a greater reduction in dyspareunia (painful intercourse) with an average change of -1.0 units on a scale, compared to -0.7 units for DMPA-SC. Regarding bone mineral density (BMD) of the spine at Week 24, Elagolix 150 mg once daily resulted in a -0.11% change from baseline, indicating less bone loss than the -0.99% seen with DMPA-SC.
Another study (NCT00619866) compared Elagolix to placebo. Patients taking Elagolix 150 mg experienced an average reduction of -0.66 units in monthly mean dysmenorrhea score, and those on Elagolix 250 mg had an average reduction of -0.65 units, both significantly greater than the -0.24 units seen with placebo. Both Elagolix doses also led to a greater reduction in the percentage of days requiring any analgesic use, with an average reduction of 10.6% for Elagolix 150 mg and 10.4% for Elagolix 250 mg, versus 5.6% for placebo. At Week 12, Elagolix 150 mg had a minimal impact on spinal BMD (-0.045% change), while Elagolix 250 mg showed a -0.937% change, compared to a slight increase of 0.375% for placebo.
In a third trial (NCT00797225) involving placebo and leuprorelin, Elagolix 150 mg and 250 mg doses reduced dysmenorrhea by -1.29 and -1.47 units respectively, compared to -1.03 units for placebo. Leuprorelin showed a greater reduction at -1.75 units. However, Elagolix doses generally resulted in less bone loss than leuprorelin. For instance, at Week 12, Elagolix 150 mg led to a -1.053% change in spinal BMD, and Elagolix 250 mg to a -0.799% change, while leuprorelin resulted in a -1.633% change. Patients on leuprorelin also experienced more hot flashes (median 1.73 per day) compared to Elagolix (median 0.00-1.10 per day) or placebo (median 0.00-0.11 per day).
A fourth study (NCT00973973) further demonstrated the efficacy of Elagolix 150 mg compared to placebo. Patients on Elagolix experienced an average reduction of 18.6% in days requiring any analgesic use during the double-blind phase, compared to 7.5% for placebo. Additionally, nearly half (49.1%) of patients on Elagolix reported feeling "much improved" or "very much improved" on a global impression scale, which was double the rate seen with placebo (24.4%).
Elagolix for Uterine Fibroids
In a study (NCT01441635) of pre-menopausal women with heavy uterine bleeding and uterine fibroids, various doses of Elagolix were evaluated. A significant number of patients achieved a reduction in menstrual blood loss (MBL) to less than 80 mL and a 50% or greater reduction from baseline. For example, 97% of patients on Elagolix 300 mg twice daily met this composite endpoint, compared to 33% on placebo in that cohort. Across different Elagolix doses, this response rate ranged from 74% to 97%, while placebo rates ranged from 13% to 33%.
Elagolix treatment also led to clinically meaningful improvements in hemoglobin levels. Patients on Elagolix experienced an increase in hemoglobin concentration ranging from 0.92 to 1.54 g/dL, while placebo groups showed changes from -0.43 to 0.31 g/dL. Furthermore, Elagolix significantly reduced uterine volume. Between 25% and 69% of patients on Elagolix achieved a 25% or greater reduction in uterine volume, compared to 7% to 11% on placebo.
Currently Recruiting Trials
Clinical trials are currently underway for Elagolix, exploring its potential benefits across various conditions. These studies aim to gather more information about how Elagolix works, its effectiveness, and its safety profile, often comparing it to existing treatments or a placebo.
One active Phase 4 study, NCT07532876, sponsored by Pak Emirates Military Hospital, is comparing Elagolix directly with oral contraceptive pills (OCPs) for reducing pelvic pain associated with endometriosis. This trial seeks to enroll 90 participants to provide clear evidence that can help doctors make more personalized treatment decisions for women with endometriosis.
Penn State University is sponsoring a Phase 4 trial, NCT06798571, investigating the role of menopause in thermoregulation. This study, targeting 24 participants, examines how different estrogen levels in premenopausal and postmenopausal women affect their body's response to heat, a critical area given increasing heat wave frequency and its impact on older adults.
A Phase 3 clinical trial, NCT06375811, led by Yale University, is evaluating Elagolix as a pre-IVF treatment for women with endometriosis and infertility. This study plans to enroll 297 participants, comparing a 60-day course of an oral GnRH antagonist (like Elagolix) to a placebo or standard IVF care, with the primary goal of assessing live birth rates.
Also sponsored by Yale University, an Early Phase 1 study, NCT03746535, is exploring cardiovascular disease risk in women with endometriosis. This trial, with an enrollment target of 40 participants, is testing the hypothesis that estrogen suppression may affect endothelial function in women with endometriosis.
Where to Participate
Participation in clinical trials for Elagolix is available across several locations, offering opportunities for eligible individuals to contribute to medical research. Currently, there are 7 sites spread across 6 cities and 6 states actively recruiting participants.
Top recruiting locations include:
- New Haven, Connecticut (2 sites)
- Aurora, Colorado (1 site)
- Chicago, Illinois (1 site)
- Baltimore, Maryland (1 site)
- Morrisville, North Carolina (1 site)
- University Park, Pennsylvania (1 site)
General eligibility criteria for these trials typically include women aged 18 to 64 years. Many studies welcome healthy volunteers, while others focus on individuals with specific conditions like endometriosis or those experiencing menopause. All trials are designed for female participants and do not involve children.
Development Timeline
The journey of Elagolix began with its first clinical trial on February 21, 2007, marking the start of extensive research into its therapeutic potential. Since then, a total of 33 trials have been initiated, enrolling over 9,522 participants to investigate its effects.
Early development initially focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the research pipeline for Elagolix significantly expanded, driven primarily by AbbVie, which has sponsored 17 trials, including those under its prior name, Abbott. This expansion led to investigations into a broader range of gynecological and endocrine conditions.
The drug's development progressed through various phases, with a strong emphasis on later-stage studies, including 15 Phase 3 trials and 9 Phase 2 trials. Elagolix's potential was explored for conditions such as Heavy Menstrual Bleeding, Infertility, Endometriosis, Pain, Fibroid Uterus, and Menopause. More recent trials have also looked into areas like Aging, Polycystic Ovary Syndrome, and Mild Autonomous Cortisol Excess, demonstrating a continuous effort to understand the full scope of Elagolix's therapeutic applications, with the latest trial projected to conclude in 2026.