Elagolix in endometriosis-related pain: a profile of its use as approved in the USA

Elagolix (Orilissa™), an oral non-peptide gonadotropin-releasing hormone receptor antagonist, is approved for the management of moderate to severe pain associated with endometriosis in the USA and Canada. It reduces levels of gonadotropins, thereby suppressing ovarian sex hormones, ovulation, and endometrial proliferation. In phase 3 trials in women with moderate to severe endometriosis-related pain, elagolix 150 mg once daily and 200 mg twice daily improved clinical response rates for dysmenorrhea and non-menstrual pelvic pain to a significantly greater extent than placebo at 3 and 6 months of treatment. Improvements from baseline in several other endometriosis pain-related outcomes were also better with elagolix than with placebo, with the benefits of treatment being maintained with treatment for an additional 6 months in extension studies. Elagolix is generally well tolerated, with most adverse events being of mild to moderate severity. However, elagolix is associated with a dosage-dependent risk of bone loss, which limits its duration of therapy, use in at-risk patients, and concomitant use with certain drugs. Similar content being viewed by others

Greene AD, Lang SA, Kendziorski JA, et al. Endometriosis: where are we and where are we going? Reproduction. 2016;152(3):R63–R78. Ferrero S, Barra F, Maggiore ULR. Current and emerging therapeutics for the management of endometriosis. Drugs. 2018;78:995–1012. Giudice LC. Endometriosis. N Engl J Med. 2010;362(25):2389–98. Ezzati M, Carr BR. Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Womens Health (Lond). 2015;11(1):19–28. Ferrero S, Esposito F, Abbamonte LH, et al. Quality of sex life in women with endometriosis and deep dyspareunia. Fertil Steril. 2005;83(3):573–9. Nnoaham KE, Hummelshojc L, Webster P, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366–73. Soliman AM, Yang H, Du EX, et al. The direct and indirect costs associated with endometriosis: a systematic literature review. Hum Reprod. 2016;31(4):712–22. Lamb YN. Elagolix: first global approval. Drugs. 2018;78(14):1501–8. Ng J, Chwalisz K, Carter DC, et al. Dose-dependent suppression of gonadotropins and ovarian hormones by elagolix in healthy premenopausal women. J Clin Endocrinol Metab. 2017;102(5):1683–91. Struthers RS, Nicholls AJ, Grundy J, et al. Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix. J Clin Endocrinol Metab. 2009;94(2):545–51. Orilissa™ (elagolix) tablets, for oral use: US prescribing information. North Chicago (IL): AbbVie Inc.; 2018. Orilissa™ (elagolix) 150 mg and 200 mg tablets: Canadian product monograph. St-Laurent (QC): AbbVie Corporation; 2018. Archer D, Ng J, Chiu YL, et al. Dose-dependent suppression of ovulation and ovarian activity by elagolix in healthy premenopausal women [abstract]. Reprod Sci. 2017;24(1 Suppl 1):140A. Acs N, O’Brien C, Jiang P, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist: results from a phase 2, randomized controlled study. J Endometr Pelvic Pain Disord. 2015;7(2):56–62. Diamond MP, Carr B, Dmowski WP, et al. Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study. Reprod Sci. 2014;21(3):363–71. Carr B, Dmowski WP, O’Brien C, et al. Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density. Reprod Sci. 2014;21(11):1341–51. Ng J, Salem A, Carter D, et al. Effect of the coadministration of ketoconazole on the pharmacokinetics and safety of elagolix in healthy premenopausal females [abstract no. PI-090]. Clin Pharmacol Ther. 2016;99(Suppl 1):S55. Ng J, Salem A, Carter D, et al. Effects of the coadministration of multiple doses of elagolix on the pharmacokinetics and safety of digoxin in healthy women [abstract]. Clin Pharmacol Drug Dev. 2017;6(Suppl 1):54–5. Polepally AR, Dufek MB, Dharia SP, et al. Drug-drug interaction of midazolam with elagolix, a novel oral GnRH antagonist: analyses of data from two studies [abstract]. In: 2017 Annual Meeting of the American College of Clinical Pharmacology. 2017. Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med. 2017;377(1):28–40. Diamond MP, Simon J, Lessey BA, et al. The effect of elagolix on the endometrium: safety results from two randomized, placebo-controlled studies in women with endometriosis-associated pain [abstract no. O-232]. Fertil Steril. 2016;106(3 Suppl):e94–5. Ng J, Klein CE, Duan WR, et al. Pharmacokinetics of elagolix, a novel oral gonadotropin-releasing hormone (GNRH) antagonist administered to female subjects with hepatic impairment [abstract no. PII-110]. Clin Pharmacol Ther. 2015;97 (Suppl 1):S93. Winzenborg I, Nader A, Polepally AR, et al. Population pharmacokinetics of elagolix in healthy women and women with endometriosis. Clin Pharmacokinet. 2018;57(10):1295–306. Carr B, Giudice L, Dmowski WP, et al. Elagolix, an oral GnRH antagonist for endometriosis-associated pain: a randomized controlled study. J Endometr Pelvic Pain Disord. 2013;5(3):105–15. Surrey E, Taylor HS, Giudice L, et al. Long-term outcomes of elagolix in women with endometriosis: results from two extension studies. Obstet Gynecol. 2018;132(1):147–60. Leyland N, Surrey E, Soliman AM, et al. Baseline burden of endometriosis-associated pain among women in two phase 3 elagolix studies [abstract no. 10Q]. Obstet Gynecol. 2018;131(Suppl 1):186S–7S. Singh S, Lessey BA, Martinez M, et al. Reductions in endometriosis-associated pain among elagolix-treated women are consistent across a range of baseline characteristics [abstract no. O-198]. Fertil Steril. 2018;110(Suppl 4):e84. Taylor HS, Diamond M, Surrey E, et al. Decreased rescue analgesic use with elagolix treatment in women with endometriosis-associated pain [abstract no. 35G]. Obstet Gynecol. 2018;131(Suppl 1):84S–5S. Leyland N, Taylor HS, Archer DF, et al. Elagolix reduced dyspareunia and improved health-related quality of life in premenopausal women with endometriosis-associated pain [abstract no. O-193]. Fertil Steril. 2018;110 (4 Suppl):e82-e83. Diamond M, Soliman AM, Castelli-Haley J, et al. Elagolix reduces fatigue in patients with moderate-to-severe endometriosis pain [abstract no. 34G]. Obstet Gynecol. 2018;131(Suppl 1):84S. Agarwal SK, Soliman AM, Schwefel B, et al. Impact of elagolix on health-related quality of life among patients with moderate to severe endometriosis-associated pain: analysis of EQ-5D-5L data from a phase III randomized controlled trial [abstract no. PIH25]. Value Health. 2018;21(Suppl 1):S144–S145. Diamond M, Soliman AM, Snabes MC, et al. Productivity gains associated with treatment with elagolix for endometriosis-associated pain [abstract no. PIH24]. Value Health. 2018;21(Suppl 1):S144. Archer D, Flores OA, Leyland N, et al. Bone turnover changes in women treated with elagolix or placebo during the Elaris EM-I and EM-II trials who did not continue in the extension studies [abstract no. O-25]. Fertil Steril. 2018;110(4 Suppl):e12. Ng J, Salem A, Carter D, et al. Effects of the coadministration of single and multiple doses of rifampin on the pharmacokinetics and safety of elagolix in healthy premenopausal females [abstract no. PI-089]. Clin Pharmacol Ther. 2016;99(Suppl 1):S54–S55

The manuscript was reviewed by S. Ferrero, Academic Unit of Obstetrics and Gynecology, IRCCS Ospedale Policlinico San Martino, Genova, Italy, and others. During the peer review process, AbbVie Inc., the marketing-authorization holder of elagolix, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit. Author information Authors and Affiliations Corresponding author Ethics declarations Funding The preparation of this review was not supported by any external funding. Conflict of interest K.A. Lyseng-Williamson is an employee of Adis/Springer, is responsible for the article content and declares no conflicts of interest. Rights and permissions About this article Cite this article Lyseng-Williamson, K.A. Elagolix in endometriosis-related pain: a profile of its use as approved in the USA. Drugs Ther Perspect 35, 110–118 (2019). https://doi.org/10.1007/s40267-019-00606-y Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s40267-019-00606-y