Women’s Health · Clinical trials
Endometriosis Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About endometriosis — and why its trials are hard
Endometriosis is a chronic, oestrogen-dependent inflammatory disorder in which endometrium-like tissue grows outside the uterus, causing dysmenorrhoea, chronic pelvic pain, dyspareunia and subfertility in roughly 10% of reproductive-age women. Diagnosis is frequently delayed by years, and management remains symptom-directed rather than curative. First-line medical therapy relies on suppressing ovarian oestrogen: combined hormonal contraceptives and progestins, injectable GnRH agonists (leuprolide) and, historically, danazol. The pivotal modern advance is the oral GnRH antagonist elagolix (Orilissa), FDA-approved in 2018 after the ELARIS EM-I/EM-II programme, delivering dose-dependent reductions in dysmenorrhoea. Relugolix combination therapy (Myfembree) followed for moderate-to-severe pain. These agents produce hypo-oestrogenism, so add-back or duration limits mitigate bone loss and vasomotor effects. No therapy eradicates disease or reliably preserves fertility, and recurrence after stopping treatment is common, leaving substantial unmet need for non-hormonal, disease-modifying and fertility-sparing options.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Elagolix (Orilissa) | 2018 | Moderate-to-severe pain associated with endometriosis | ELARIS EM-I (Taylor et al., NEJM 2017) and ELARIS EM-II | Proportion of dysmenorrhoea and non-menstrual pelvic pain responders at 3 months (Daily Assessment of Endometriosis Pain scale) | ELARIS EM-I dysmenorrhoea responders: 75.8% (200 mg BID) and 46.4% (150 mg QD) vs 19.6% placebo; non-menstrual pelvic pain responders: 54.5% and 50.4% vs 36.5% placebo (all P<0.001) |
| Relugolix + estradiol + norethindrone acetate (Myfembree) | 2022 | Moderate-to-severe pain associated with endometriosis (approved indication added 2022) | SPIRIT 1 and SPIRIT 2 phase 3 trials | Proportion of responders for dysmenorrhoea and non-menstrual pelvic pain at week 24 with no increase in analgesic use | Approximately 75% dysmenorrhoea responders vs ~27% placebo, and ~59% non-menstrual pelvic pain responders vs ~40% placebo (P<0.0001) |
| Leuprolide acetate (Lupron Depot) | 1990 | GnRH agonist for management of endometriosis and associated pain | Multiple randomized controlled trials vs danazol and placebo | Reduction in pelvic pain and endometriotic lesion scores | Significant reduction in dysmenorrhoea and pelvic pain comparable to danazol; requires add-back therapy to limit bone mineral density loss (unverified exact response percentages) |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in endometriosis development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Infliximab (anti-TNF-alpha) — Koninckx et al. randomized placebo-controlled trial (Human Reproduction 2008) | No significant reduction in endometriosis-associated pelvic pain versus placebo | TNF blockade did not translate to clinical pain benefit; anti-inflammatory hypothesis not supported, and infection risk discouraged further development |
| Asoprisnil (selective progesterone receptor modulator) — Phase 2 endometriosis and fibroid programme | Development discontinued despite pain reduction signals | Non-physiological endometrial changes (progesterone-receptor-modulator-associated endometrial changes) raised safety concerns, halting the programme |
Choosing the right endpoint
Primary endpoints that matter in endometriosis trials
- Dysmenorrhoea responder rate — Proportion achieving a clinically meaningful reduction in menstrual pelvic pain, typically via the Daily Assessment of Endometriosis Pain scale, with no increase in rescue analgesia
- Non-menstrual pelvic pain responder rate — Proportion with reduced pain on non-bleeding days, capturing the chronic pain burden distinct from cyclical dysmenorrhoea
- Dyspareunia — Deep pain with intercourse, an important secondary patient-reported endpoint
- Analgesic (opioid) use — Co-primary safety/efficacy criterion requiring no increase in rescue medication to count as a responder
- Bone mineral density — Key safety endpoint given hypo-oestrogenic mechanism; monitored to bound treatment duration or justify add-back
How iNGENū runs endometriosis trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Endometriosis clinical trials — FAQs
Is any endometriosis drug curative?
How does elagolix differ from leuprolide?
Why are these treatments time-limited?
Ready to discuss your endometriosis trial?
Talk to our physician-led team about an FDA-ready, cost-efficient trial design.
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