Elagolix
| Evidence Level: L2 | Predicted Indications: 1 |
Table of Contents
Elagolix: From Its Original Use to Amenorrhea
One-Sentence Summary
Elagolix is an oral GnRH receptor antagonist marketed in the US as Orilissa. The TxGNN model predicts it may be effective for amenorrhea. This is supported by 3 Phase 2 clinical trials and 4 publications, all in related conditions (uterine fibroids, endometriosis), none in amenorrhea itself. Amenorrhea is better understood as an expected pharmacodynamic effect of the drug than as a treatable disease indication.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.75% |
| Evidence Level | L2 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 2 license entries (both NDA210450, so 1 unique NDA) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Elagolix blocks GnRH receptors in the pituitary. This lowers LH and FSH, which in turn lowers ovarian estradiol and progesterone. As a result, menstrual bleeding is reduced or stopped in a dose-dependent way.
Amenorrhea is therefore an expected effect of elagolix, and it is reported as an efficacy outcome in fibroid and endometriosis trials. The high TxGNN score most likely reflects this graph-level link between the drug and menstrual disorders.
The prediction should be read with caution. In the supporting trials, suppressing menses is the intended treatment effect, not a condition being treated. No trial enrolled patients with amenorrhea as the target condition. The original indication is not listed in the source data, and several trial and paper titles are truncated, so relevance grades should be confirmed against the full records.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01817530 | Phase 2b | Completed | 571 | Randomized, double-blind, placebo-controlled. Elagolix alone and with add-back therapy vs placebo for heavy menstrual bleeding with uterine fibroids. Most relevant trial (Grade A) because bleeding suppression and amenorrhea rates are directly relevant endpoints. |
| NCT01441635 | Phase 2a | Completed | 271 | Proof-of-concept study of elagolix vs placebo for uterine bleeding, fibroid volume, and uterine volume in premenopausal women aged 20-49 with heavy uterine bleeding (Grade B). |
| NCT00797225 | Phase 2 | Completed | 174 | Randomized, double-blind study of elagolix (NBI-56418) vs placebo and leuprorelin in endometriosis, 3 months plus 3 months of elagolix. Only indirectly relevant (Grade C). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37769311 | 2023 | RCT | Obstetrics and Gynecology | Safety and efficacy of elagolix 150 mg once-daily monotherapy for heavy menstrual bleeding with uterine leiomyomas. |
| 32702363 | 2021 | Post-hoc analysis of RCT data | American Journal of Obstetrics and Gynecology | Predictors of response to elagolix with add-back therapy in heavy menstrual bleeding with uterine fibroids. |
| 37103532 | 2023 | Review | Obstetrics and Gynecology | Overview of oral GnRH antagonists for uterine leiomyomas, covering efficacy and safety with add-back or partial-suppression dosing. |
| 31695514 | 2019 | Review | International Journal of Women’s Health | Short report on emerging efficacy data for elagolix as an oral treatment for uterine fibroids. |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA210450 | Orilissa (AbbVie Inc.) | Tablet, film coated (oral) | Not provided in the source data |
The source lists this NDA twice with identical details; it is shown once here.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence consists of Phase 2 trials and reviews in related conditions, with none in amenorrhea as a disease. Amenorrhea is mainly an intended pharmacodynamic effect of GnRH antagonism, so there is no clear unmet-need indication to develop.
To proceed, the following is needed:
- A clear clinical definition of the target population, since amenorrhea is the expected result of treatment in most settings.
- Full trial records to confirm the truncated titles and endpoints, especially amenorrhea rates in NCT01817530.
- The US package insert (warnings, contraindications) and the approved indication text, which are missing from the source data.
- Confirmed mechanism of action data from DrugBank.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.