Women’s Health · Clinical trials
Uterine Fibroids 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 uterine fibroids — and why its trials are hard
Uterine fibroids (leiomyomas) are benign, oestrogen- and progesterone-responsive smooth-muscle tumours affecting a majority of women by age 50, with disproportionate burden and earlier, more severe disease in Black women. Symptoms include heavy menstrual bleeding, anaemia, pelvic pressure, bulk symptoms and reproductive dysfunction. Historically management was surgical (myomectomy, hysterectomy) or interventional (uterine artery embolisation), with limited durable medical options. The therapeutic landscape shifted with oral GnRH antagonist combination therapies that suppress ovarian steroid production while providing hormonal add-back to preserve bone and control vasomotor effects. Elagolix combination (Oriahnn) and relugolix combination (Myfembree) were both FDA-approved after phase 3 programmes (ELARIS UF and LIBERTY) demonstrating large reductions in menstrual blood loss. Tranexamic acid and leuprolide provide additional bleeding control, the latter often used preoperatively. Medical therapy manages symptoms and bleeding but does not eliminate fibroids, which can regrow after cessation, sustaining demand for uterine-sparing, durable and fertility-compatible 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 |
|---|---|---|---|---|---|
| Relugolix + estradiol + norethindrone acetate (Myfembree) | 2021 | Heavy menstrual bleeding associated with uterine fibroids in premenopausal women | LIBERTY 1 and LIBERTY 2 (Al-Hendy et al., NEJM 2021) | Proportion of responders achieving menstrual blood loss volume <80 mL AND >=50% reduction from baseline over the last 35 days of treatment (alkaline hematin method) | 71.7% of relugolix combination patients were responders vs 15.7% placebo at week 24 (P<0.0001 in each trial) |
| Elagolix + estradiol + norethindrone acetate (Oriahnn) | 2020 | Heavy menstrual bleeding associated with uterine fibroids in premenopausal women | ELARIS UF-1 and ELARIS UF-2 (Schlaff et al., NEJM 2020) | Proportion of responders with menstrual blood loss <80 mL AND >=50% reduction from baseline at final month | Approximately 68.5% (UF-1) and 76.5% (UF-2) responders on elagolix combination vs ~8.7% and ~10% placebo (P<0.001) |
| Tranexamic acid (Lysteda) | 2009 | Cyclic heavy menstrual bleeding (used in fibroid-associated bleeding) | Phase 3 randomized placebo-controlled trials | Reduction in menstrual blood loss | Roughly 40% reduction in menstrual blood loss versus placebo (antifibrinolytic; does not shrink fibroids) |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in uterine fibroids development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Ulipristal acetate (Esmya, selective progesterone receptor modulator) — PEARL I-IV programme (approved in EU/Canada; US new drug application not approved) | Reduced bleeding and fibroid volume but did not achieve US approval and use was severely restricted in Europe | Rare but serious cases of drug-induced liver injury including liver failure requiring transplant prompted regulatory restriction; FDA did not approve for fibroids |
| Vilaprisan (selective progesterone receptor modulator) — ASTEROID phase 2/3 programme (Bayer) | Development halted despite efficacy on bleeding and fibroid volume | Non-clinical (animal) toxicology findings led to suspension and eventual discontinuation of the programme |
Choosing the right endpoint
Primary endpoints that matter in uterine fibroids trials
- Menstrual blood loss responder rate — Co-primary standard: MBL <80 mL and >=50% reduction from baseline measured objectively by the alkaline hematin method
- Absolute menstrual blood loss (mL) — Quantitative change from baseline; <80 mL is the clinical threshold defining normal menses
- Haemoglobin/anaemia correction — Improvement in haemoglobin reflects clinically relevant reduction of bleeding-related anaemia
- Fibroid and uterine volume — Imaging-based measure of anatomic burden; medical therapy variably reduces volume and effect may reverse on stopping
- Bone mineral density — Safety endpoint driving the estradiol/norethindrone add-back in GnRH antagonist combination products
How iNGENū runs uterine fibroids 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
Uterine Fibroids clinical trials — FAQs
Do GnRH antagonist combinations shrink fibroids permanently?
Why include estradiol and norethindrone in the pill?
Is tranexamic acid a hormonal treatment?
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