Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature

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This review examined Elagolix, a GnRH antagonist for endometriosis, finding promising efficacy, safety, and tolerability in Phase II trials with potential for Phase III results to confirm its value.

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This paper is a literature review assessing clinical studies of the oral GnRH antagonist elagolix for endometriosis, focusing on pharmacodynamic activity, safety, and efficacy. The authors searched PubMed and ScienceDirect for English-language clinical studies using terms related to endometriosis treatment and GnRH antagonists, identifying five studies: one phase 1 study in healthy premenopausal women evaluating gonadotropin and estradiol inhibition plus pharmacokinetics and safety, and two phase II studies in patients with endometriosis; two phase III trials were reported as completed but not yet detailed. The review concludes that GnRH antagonists may offer oral administration and a lower incidence of adverse events, and that published phase II results show promising efficacy, safety, and tolerability while phase III findings were expected to clarify elagolix’s value for endometriosis-related pain. This paper is centrally about endometriosis — it reviews the development and trial evidence for elagolix to treat endometriosis symptoms and pain.

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Abstract

PurposeLimitated studies have reported the efficacy of GnRH antagonist on endometriosis symptoms. The aim of our study was to review all available trials to investigate the medical treatment of endometriosis with only GnRH antagonists, with special attention to pharmacodynamic activity, safety, and efficacy.MethodsPub Med and Sciencedirect database were searched using terms of "endometriosis treatment", "GnRH antagonist", and "Elagolix". The search was limited to clinical studies published in English. Title and abstract were screened to identify relevant articles.ResultsFive studies covering use of GnRH antagonist were found. A phase 1 study evaluated the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single dose and 7 day elagolix administration to healthy premenopausal women; two phase II studies evaluated efficacy in patient with endometriosis. Moreover, there are two Phase III clinical trials just completed.ConclusionGnRH antagonists may have the advantage of oral administration and lower incidence of adverse events. Currently, only Phase II studies have been published demonstrating promising results in terms of efficacy, safety, and tolerability. From the results of the phase III studies, elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain.
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Abstract

Purpose Limitated studies have reported the efficacy of GnRH antagonist on endometriosis symptoms. The aim of our study was to review all available trials to investigate the medical treatment of endometriosis with only GnRH antagonists, with special attention to pharmacodynamic activity, safety, and efficacy.

Methods

Pub Med and Sciencedirect database were searched using terms of “endometriosis treatment”, “GnRH antagonist”, and “Elagolix”. The search was limited to clinical studies published in English. Title and abstract were screened to identify relevant articles.

Results

Five studies covering use of GnRH antagonist were found. A phase 1 study evaluated the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single dose and 7 day elagolix administration to healthy premenopausal women; two phase II studies evaluated efficacy in patient with endometriosis. Moreover, there are two Phase III clinical trials just completed.

Conclusion

GnRH antagonists may have the advantage of oral administration and lower incidence of adverse events. Currently, only Phase II studies have been published demonstrating promising results in terms of efficacy, safety, and tolerability. From the results of the phase III studies, elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain. Similar content being viewed by others

References

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Curr Drug Ther 10(2):91–94.13 Ezzati M, Carr BR (2015) Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Womens Health (Lond) 11(1):19–28. Melis GB, Neri M, Corda V et al (2016) Overview of elagolix for the treatment of endometriosis. Expert Opin Drug Metab Toxic 12(5):581–588. Struthers RS, Nicholls AJ, Grundy J et al (2009) Suppression of gonadotropin and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix. J Clin Endocrinol Metab 94(2):545–551 Carr BR (2008) Endometriosis. In: Hoffman BL, Schorge JO, Schaffer JI et al (eds) Williams gynecology. 2nd edn. Chapter. McGraw-Hill, 10. New York Diamond MP, Carr B, Dmowski WP et al (2014) Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study. Reprod Sci 21(3):363–371. Carr B, Giudice L, Dmowsky WP et al (2013) Elagolix, an oral GnRH antagonist for endometriosis-associated pain: a randomized controlled study. J Endometr Pelvic Disord 5(3):105–115 Surrey E, Giudice LC, Lessey BA et al (2016) Use of elagolix for the managment of endometriosis-associated pain: secondary efficacy results from two randomized, placebo-controlled studies. Fertil Steril 3:e268–e269. Taylor HS, Giudice LC, Lessey BA et al (2016) Elagolix, an oral gonadotropin-realising hormone antagonist, for the management of endometriosis-associated pain: safety and efficacy results from two double-blind, randomized, placebo controlled studies. Fertil Steril 106(3):e271 Taylor HS, Surrey E, Soliman AM et al (2016) The impact of elagolix on quality of life in women with endometriosis-associated pain: results from two randomized, placebo-controlled studies using the endometriosis health profile questionnaire. Fertil Steril 106(3):e93 Diamond MP, Simon J, Lessey BA et al (2016) The effect of elagolix on the endometrium: safety results from two randomized, placebo-controlled studies in women with endometriosis-associated pain. Fertil Steril 106(3):e94–e95 Archer DF, Watts N, Gallagher C et al (2016) The effect of elagolix on bone mineral density: safety results from two randomized, placebo-controlled studies in women with endometriosis associated pain. Fertil Steril 106(3):e276–e277 Angioni S, Cofelice V, Pontis A, Tinelli R, Socolov R (2014) New trends of progestins treatment of endometriosis. Gynecol Endocrinol 30(11):769–773 Author contributions Protocol/project development Angioni S, Melis GB. Data collection or management Pontis A, Nappi L. Data analysis Pontis A, Paoletti AM. Manuscript writing Pontis A, Sorrentino F. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest Authors declare that have not conflict of interest. Ethical approval This article does not contain any studies with human participants or animals part performed by any of the authors. Rights and permissions About this article Cite this article Alessandro, P., Luigi, N., Felice, S. et al. Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature. Arch Gynecol Obstet 295, 827–832 (2017). https://doi.org/10.1007/s00404-017-4328-6 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-017-4328-6

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Gonadotropin-Releasing Hormone Hormone Antagonists Hydrocarbons, Fluorinated Pyrimidines Adult Endometriosis Endometriosis Estradiol Estradiol Female Gonadotropin-Releasing Hormone Gonadotropins Gonadotropins Hormone Antagonists Humans Hydrocarbons, Fluorinated Pain Pain Pain

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