FOGSI Expert Consensus Review Redefines Landscape of Endometriosis Management with Elagolix: 5 Key Takeaways

The expert consensus is based on a review of available global and Indian clinical evidence, assessing the efficacy, safety profile, and the potential role of Elagolix as a long-term medical management for endometriosis-associated pain.

Endometriosis affects nearly 196 million women globally and approximately 42 million women in India. Despite multiple available medical therapies, long-term disease control remains challenging, as conventional options such as NSAIDs, combined oral contraceptives(COC), progestins and injectable GnRH agonists are often limited by inadequate symptom relief, flare reactions, hypoestrogenic adverse effects, bone mineral density loss, and poor long-term tolerability.

Elagolix is an oral, non-peptide GnRH receptor antagonist that provides rapid, dose-dependent suppression of ovarian oestradiol without the initial flare effect seen with GnRH agonists, offering a mechanism-driven clinical advantage that allows individualisation of therapy based on disease severity and safety considerations.

The consensus draws on evidence from pivotal Phase III ELARIS trials (EM-I and EM-II), which evaluated Elagolix in women with surgically confirmed moderate-to-severe endometriosis-associated pain. These studies demonstrated statistically significant reductions in dysmenorrhoea and non-menstrual pelvic pain (NMPP) with both 150 mg once-daily and 200 mg twice-daily dosing, with sustained benefits observed in long-term extension studies. Additional Indian Phase III data showed Elagolix to be non-inferior to Dienogest in pain reduction, with a favourable tolerability profile.

Elagolix in Endometriosis Therapy-Top 5 Key Takeaways:

1. Elagolix-Emerging Potential First line medical therapy: Elagolix is the first oral, non-peptide Gonadotropin-releasing Hormone (GnRH) antagonist approved for the management of moderate-to-severe endometriosis-associated pain, and based on the available global and Indian clinical evidence, the expert consensus noted that it may be considered as an emerging, potential first-line medical therapy for appropriately selected patients.It operates by providing competitive, reversible GnRH receptor blockade in the anterior pituitary, leading to rapid, dose-dependent suppression of ovarian estradiol and progesterone production. Critically, unlike GnRH agonists, this mechanism avoids the initial clinical symptom "flare" effect.

2. Dose-Dependent Estradiol Targeting and Treatment Duration Allowing Safe Use: Elagolix dosing leverages the "therapeutic window" (30–50 pg/mL) to balance efficacy and bone health.

• The 150 mg once daily (OD) dose achieves partial suppression (~42 pg/mL), which is effective for lesion regression while maintaining bone safety, approved for use up to 24 months without the need for add-back therapy.

• The 200 mg twice daily (BID) dose provides near-complete suppression (~12 pg/mL) for stronger symptomatic control in severe pain (e.g., severe dysmenorrhoea, dyspareunia), though this dose is approved for continuous use up to 6 months due to increased Bone Mineral Density (BMD) concerns.

3. Superior Efficacy in Core Pain Symptoms: Pivotal Phase III trials (Elaris EM-I and EM-II) demonstrated significant and sustained reduction in both dysmenorrhoea (DM) and non-menstrual pelvic pain (NMPP) over 6 to 12 months. A systematic review and network meta-analysis further established that Elagolix provides greater relief from dysmenorrhoea compared to other pharmacological interventions, including injectable GnRH antagonists/agonists, progestins, and combined oral contraceptives (COCs).

Table 1: Elagolix Efficacy in ELARIS EM-1 & EM-II Trials

4. Favorable Safety and Bone Health Profile: Elagolix is generally well tolerated, with the most common adverse events being dose-dependent and typically mild-to-moderate, such as hot flushes, headache, and nausea. Compared to Leuprolide (a GnRH agonist), Elagolix is associated with significantly lower rates of hot flushes and depression. The BMD decline observed is dose- and duration-dependent (e.g., mean −0.63% at the lumbar spine for 150 mg OD at 12 months), which is less pronounced than with Leuprolide, and the BMD values tend to return towards baseline following cessation of treatment.

5. Broad Therapeutic Utility & Patient Symptom Benefits: Beyond mitigating pain, Elagolix significantly enhances disease-specific Quality of Life scores (EHP-30) and reduces associated fatigue. Clinical trials also support its utility in gynecological conditions beyond endometriosis, including effectiveness in controlling heavy menstrual bleeding (HMB) associated with uterine fibroids and potential benefits in adenomyosis. Furthermore, oral Elagolix is a promising, less invasive alternative to injectable GnRH antagonists in Assisted Reproductive Technology (ART) protocols for reliable prevention of premature LH surges during controlled ovarian stimulation

References

FOGSI Endometriosis Expert Consensus Document – Review of global and Indian evidence on Elagolix in endometriosis management.