325
Views
3
CrossRef citations to date
0
Altmetric
Drug Evaluation

The potential role of elagolix for treating uterine bleeding associated to uterine myomas

ORCID Icon, ORCID Icon, , , , & ORCID Icon show all
Pages 1419-1430 | Received 16 Aug 2019, Accepted 09 Apr 2020, Published online: 13 May 2020

References

  • Donnez J , Dolmans MM. Uterine fibroid management: from the present to the future. Hum Reprod Update. 2016 Nov;22(6):665–686.
  • Zimmermann A , Bernuit D , Gerlinger C , et al. Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women. BMC Womens Health. 2012 Mar 26;12(1):6.
  • D’Alessandro G , Barra F , Ferrero S . Epidemiology and Risk Factors Of Uterine Myomas. In: Ferrero S , Barra F , editors. Uterine fibroids: epidemiology, symptoms and management. Nova science publisher; 2019. p. 1-34.
  • Sparic R , Mirkovic L , Malvasi A , et al. Epidemiology of uterine myomas: a review. Int J Fertil Steril. 2016 Jan-Mar;9(4):424–435.
  • Malik M , Norian J , McCarthy-Keith D , et al. Why leiomyomas are called fibroids: the central role of extracellular matrix in symptomatic women. Semin Reprod Med. 2010 May;28(3):169–179.
  • Tinelli A , Malvasi A , Rahimi S , et al. Myoma pseudocapsule: a distinct endocrino-anatomical entity in gynecological surgery. Gynecol Endocrinol. 2009 Oct;25(10):661–667.
  • Tinelli A , Favilli A , Lasmar RB , et al. The importance of pseudocapsule preservation during hysteroscopic myomectomy. Eur J Obstet Gynecol Reprod Biol. 2019 Dec;243:179–184.
  • Bulun SE . Tissue stem cells and uterine physiology and pathology. Semin Reprod Med. 2015 Sep;33(5):313–314.
  • Al-Hendy A , Laknaur A , Diamond MP , et al. Silencing med12 gene reduces proliferation of human leiomyoma cells mediated via Wnt/beta-catenin signaling pathway. Endocrinology. 2017 Mar 1;158(3):592–603.
  • Corachan A , Ferrero H , Aguilar A , et al. Inhibition of tumor cell proliferation in human uterine leiomyomas by vitamin D via Wnt/beta-catenin pathway. Fertil Steril. 2019 Feb;111(2):397–407.
  • Moravek MB , Yin P , Ono M , et al. Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications. Hum Reprod Update. 2015 Jan-Feb;21(1):1–12.
  • Marsh EE , Bulun SE . Steroid hormones and leiomyomas. Obstet Gynecol Clin North Am. 2006 Mar;33(1):59–67.
  • Kim JJ , Kurita T , Bulun SE . Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev. 2013 Feb;34(1):130–162.
  • Ishikawa H , Ishi K , Serna VA , et al. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology. 2010 Jun;151(6):2433–2442.
  • Ciarmela P , Islam MS , Reis FM , et al. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum Reprod Update. 2011 Nov-Dec;17(6):772–790.
  • Lagana AS , Vergara D , Favilli A , et al. Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease. Arch Gynecol Obstet. 2017 Nov;296(5):855–867.
  • Bulun SE . Uterine fibroids. N Engl J Med. 2013 Oct 3;369(14):1344–1355.
  • Drayer SM , Catherino WH . Prevalence, morbidity, and current medical management of uterine leiomyomas. Int J Gynaecol Obstet. 2015 Nov;131(2):117–122.
  • Gupta S , Jose J , Manyonda I . Clinical presentation of fibroids. Best Pract Res Clin Obstet Gynaecol. 2008 Aug;22(4):615–626.
  • Zupi E , Centini G , Sabbioni L , et al. Nonsurgical Alternatives for Uterine Fibroids. Best Pract Res Clin Obstet Gynaecol. 2016 Jul;34:122–131.
  • Sinai Talaulikar V . Medical therapy for fibroids: an overview. Best Pract Res Clin Obstet Gynaecol. 2018 Jan;46:48–56.
  • Ciebiera M , Lukaszuk K , Meczekalski B , et al. Alternative Oral Agents in Prophylaxis and Therapy of Uterine Fibroids-An Up-to-Date Review. Int J Mol Sci. 2017 Dec 1;18(12):2586.
  • D’Alessandro G , Barra F , Evangelisti G , et al. Presurgical hormonal treatment for uterine myomas. In: Ferrero S , Barra F , editors. Uterine fibroids: epidemiology, symptoms and management. Nova Science Publisher; 2019. p. 89-117.
  • Farris M , Bastianelli C , Rosato E , et al. Uterine fibroids: an update on current and emerging medical treatment options. Ther Clin Risk Manag. 2019;15:157–178.
  • Vitale SG , Ferrero S , Caruso S , et al. Ulipristal acetate before hysteroscopic myomectomy: a systematic review. Obstet Gynecol Surv. 2020 Feb;75(2):127–135.
  • U.S. Food & Drug Administration . Drug approval package: orilissa (elagolix sodium) 2018. [cited 2020 Apr 1]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210450Orig1s000TOC.cfm
  • Lamb YN . Elagolix: first Global Approval. Drugs. 2018 Sep;78(14):1501–1508.
  • Barra F , Scala C , Ferrero S . Elagolix sodium for the treatment of women with moderate to severe endometriosis-associated pain. Drugs Today (Barc). 2019;55(4):1–10.
  • Osuga Y , Enya K , Kudou K , et al. Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Compared With Leuprorelin Injections for Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2019 Mar;133(3):423–433.
  • Osuga Y , Enya K , Kudou K , et al. Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women. Fertil Steril. 2019 Nov;112(5):922–929 e2.
  • Takeda . Uterine fibroids treatment agent (GnRH antagonists) “Rerumina for manufacturing and marketing approval in Japan of Tablets 40 mg”. 2019. [cited 2020 Apr 1]. Available from: https://www.takeda.com/jp/newsroom/newsreleases/2019/20190108-8038/
  • Di Spiezio Sardo A , Mazzon I , Bramante S , et al. Hysteroscopic myomectomy: a comprehensive review of surgical techniques. Hum Reprod Update. 2008 Mar-Apr;14(2):101–119.
  • Finco A , Centini G , Lazzeri L , et al. Surgical management of abnormal uterine bleeding in fertile age women. Womens Health (Lond). 2015 Jul;11(4):513–525.
  • Keung JJ , Spies JB , Caridi TM . Uterine artery embolization: A review of current concepts. Best Pract Res Clin Obstet Gynaecol. 2018 Jan;46:66–73.
  • Machtinger R , Fennessy FM , Stewart EA , et al. MR-guided focused ultrasound (MRgFUS) is effective for the distinct pattern of uterine fibroids seen in African-American women: data from phase III/IV, non-randomized, multicenter clinical trials. J Ther Ultrasound. 2013;1(1):23.
  • Whynott RM , Vaught KCC , Segars JH . The effect of uterine fibroids on infertility: a systematic review. Semin Reprod Med. 2017 Nov;35(6):523–532.
  • Liu Y , Zhang WW , He M , et al. Adverse effect analysis of high-intensity focused ultrasound in the treatment of benign uterine diseases. Int J Hyperthermia. 2018;35(1):56–61.
  • Lozinski T , Filipowska J , Gurynowicz G , et al. The effect of high-intensity focused ultrasound guided by magnetic resonance therapy on obstetrical outcomes in patients with uterine fibroids - experiences from the main Polish center and a review of current data. Int J Hyperthermia. 2019;36(1):582–590.
  • Chabbert-Buffet N , Esber N , Bouchard P . Fibroid growth and medical options for treatment. Fertil Steril. 2014 Sep;102(3):630–639.
  • Donnez J , Nisolle M , Grandjean P , et al. The place of GnRH agonists in the treatment of endometriosis and fibroids by advanced endoscopic techniques. Br J Obstet Gynaecol. 1992 Feb;99(Suppl 7):31–33.
  • 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 Feb;94(2):545–551.
  • Rabe T , Saenger N , Ebert AD , et al. Selective progesterone receptor modulators for the medical treatment of uterine fibroids with a focus on ulipristal acetate. Biomed Res Int. 2018;2018:1374821.
  • Barra F , Seca M , Ferrero S . Vilaprisan [Article]. Drugs Future. 2019;44(3):211–219.
  • Ciebiera M , Vitale SG , Ferrero S , et al. Vilaprisan, a new selective progesterone receptor modulator in uterine fibroid pharmacotherapy - Will it really be a breakthrough? Curr Pharm Des. 2020 Jan 26;26(3):300–309.
  • Gurusamy KS , Vaughan J , Fraser IS , et al. Medical therapies for uterine fibroids - A systematic review and network meta-analysis of randomised controlled trials. PLoS One. 2016;11(2):e0149631.
  • Ciebiera M , Meczekalski B , Lukaszuk K , et al. Potential synergism between ulipristal acetate and vitamin D3 in uterine fibroid pharmacotherapy - 2 case studies. Gynecol Endocrinol. 2019 Jun;35(6):473–477.
  • Tukun FL , Olberg DE , Riss PJ , et al. Recent development of non-peptide GnRH antagonists. Molecules. 2017 Dec 9;22(12):2188.
  • Ezzati M , Carr BR . Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Womens Health (Lond). 2015 Jan;11(1):19–28.
  • 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. 2017 Apr;295(4):827–832.
  • Ferrero S , Evangelisti G , Barra F . Current and emerging treatment options for endometriosis. Expert Opin Pharmacother. 2018 Jul;19(10):1109–1125.
  • Chen C , Wu D , Guo Z , et al. Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4 -methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor. J Med Chem. 2008 Dec 11;51(23):7478–7485.
  • Taylor HS . Use of elagolix in gynaecology. J Obstet Gynaecol Can. 2018 Jul;40(7):931–934.
  • Tafi E , Leone Roberti Maggiore U , Alessandri F , et al. Advances in pharmacotherapy for treating endometriosis. Expert Opin Pharmacother. 2015;16(16):2465–2483.
  • Lukes A , Johnson B , Jones L , et al. Pharmacokinetics, pharma- codynamics, and safety of relugolix, a potent oral once-daily gonadotropin-releasing hormone (GnRH) receptor antagonist, as monotherapy and in combination with estradiol/norethindrone acetate add-back therapy [abstract no. P-287]. Hum Reprod. 2017;32(Suppl 1):i267–8.
  • Archer DF , Ng J , Chwalisz K , et al. Elagolix suppresses ovulation in a dose-dependent manner: results from a 3-month, randomized study in ovulatory women. J Clin Endocrinol Metab. 2020 Mar 1;105(3):821–832.
  • Shebley M , Polepally AR , Nader A , et al. Clinical pharmacology of elagolix: an oral gonadotropin-releasing hormone receptor antagonist for endometriosis. Clin Pharmacokinet. 2019 Nov 21.
  • Elagolix . LiverTox: clinical and research information on drug-induced liver injury. 2012; Bethesda (MD).
  • Ng J , Duan WR , Marbury T , et al. Elagolix pharmacokinetic profiles in women with renal or hepatic impairment. Clin Pharmacol Drug Dev. 2018 Nov;8(8):1053-1061.
  • Archer DF , Stewart EA , Jain RI , et al. Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study. Fertil Steril. 2017 Jul;108(1):152–160 e4.
  • Carr BR , Stewart EA , Archer DF , et al. Elagolix alone or with add-back therapy in women with heavy menstrual bleeding and uterine leiomyomas: a randomized controlled trial. Obstet Gynecol. 2018 Nov;132(5):1252–1264.
  • Mansfield PK , Voda A , Allison G . Validating a pencil-and-paper measure of perimenopausal menstrual blood loss. Womens Health Issues. 2004 Nov-Dec;14(6):242–247.
  • Spies JB , Coyne K , Guaou Guaou N , et al. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet Gynecol. 2002 Feb;99(2):290–300.
  • Schlaff WD , Ackerman RT , Al-Hendy A , et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med. 2020 Jan 23;382(4):328–340.
  • Schlaff W , Al-Hendy A , Barnhart K , et al. Elagolix reduced heavy menstrual bleeding with uterine fibroids: primary, 6-month, phase 3 results [11OP]. Obstetrics Gynecol. 2019;133:9.
  • Bradley LD , Feinberg EC , Liu R , et al. Elagolix treatment in women with uterine fibroids: secondary, 6-month, phase 3 efficacy results [11J]. Obstetrics Gynecol. 2019;133:109S.
  • AbbVie . AbbVie announces positive topline results from phase 3 extension study evaluating investigational elagolix in women with uterine fibroids 2018. [cited 2020 Apr 1]. Available from: https://news.abbvie.com/news/abbvie-announces-positive-topline-results-from-phase-3-extension-study-evaluating-investigational-elagolix-in-women-with-uterine-fibroids.htm
  • ClinicalTrials.gov . An extension study to evaluate the efficacy and safety of elagolix in premenopausal women with heavy menstrual bleeding associated with uterine fibroids. (NCT number): NCT02925494 [cited 2020 Apr 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02925494
  • ClinicalTrials.gov . Long-term safety study of elagolix in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. (NCT number): NCT03271489 [cited 2020 Apr 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03271489
  • ClinicalTrials.gov . An a study to evaluate the safety and efficacy of elagolix for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. (NCT number): NCT03886220 [cited 2020 Apr 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03886220
  • Padula AM . GnRH analogues–agonists and antagonists. Anim Reprod Sci. 2005 Aug;88(1–2):115–126.
  • Kuhnz W , Pfeffer M , Al-Yacoub G . Protein binding of the contraceptive steroids gestodene, 3-keto-desogestrel and ethinylestradiol in human serum. J Steroid Biochem. 1990 Feb;35(2):313–318.
  • Chiney MS , Ng J , Gibbs JP , et al. Quantitative assessment of elagolix enzyme-transporter interplay and drug-drug interactions using physiologically based pharmacokinetic modeling. Clin Pharmacokinet. 2019 Nov 12. DOI:10.1007/s40262-019-00833-6.
  • Lethaby A , Puscasiu L , Vollenhoven B . Preoperative medical therapy before surgery for uterine fibroids. Cochrane Database Syst Rev. 2017 Nov;15(11):CD000547.
  • Ali M , Al-Hendy A . Uterine fibroid therapy: the pharmacokinetic considerations. Expert Opin Drug Metab Toxicol. 2018 Sep;14(9):887–889.
  • Donnez J , Tatarchuk TF , Bouchard P , et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012 Feb 2;366(5):409–420.
  • Donnez J , Tomaszewski J , Vazquez F , et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med. 2012 Feb 2;366(5):421–432.
  • Donnez J , Vazquez F , Tomaszewski J , et al. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril. 2014 Jun;101(6):1565-73e1-18..
  • Donnez J , Hudecek R , Donnez O , et al. Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids. Fertil Steril. 2015 Feb;103(2):519–27 e3..
  • Ferrero S , Vellone VG , Barra F , et al. Ulipristal acetate before hysteroscopic and laparoscopic surgery for uterine myomas: help or hindrance? Gynecol Obstet Invest. 2018;14:1–13.
  • Bizzarri N , Ghirardi V , Remorgida V , et al. Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study. Eur J Obstet Gynecol Reprod Biol. 2015 Sep;192:22–26.
  • Ferrero S , Alessandri F , Vellone VG , et al. Three-month treatment with ulipristal acetate prior to laparoscopic myomectomy of large uterine myomas: a retrospective study. Eur J Obstet Gynecol Reprod Biol. 2016 Oct;205:43–47.
  • Barra F , Evangelisti G , Ferrero S . Preoperative hormonal treatment before laparoscopic approach for uterine fibroids: do we need it? J Invest Surg. 2019 Aug;28:1–3.
  • Donnez J , Arriagada P , Marciniak M , et al. Liver safety parameters of ulipristal acetate for the treatment of uterine fibroids: a comprehensive review of the clinical development program. Expert Opin Drug Saf. 2018 Dec;17(12):1225–1232..
  • European Medicines Agency . Esmya: new measures to minimise risk of rare but serious liver injury 2018. [cited 2020 Apr 1]. Available from: https://www.ema.europa.eu/en/medicines/human/referrals/esmya
  • European Medicines Agency . Suspension of ulipristal acetate for uterine fibroids during ongoing EMA review of liver injury risk. 2020. [cited 2020 Apr 1]. Available from: https://www.ema.europa.eu/en/news/suspension-ulipristal-acetate-uterine-fibroids-during-ongoing-ema-review-liver-injury-risk
  • Bouchard P , Chabbert-Buffet N , Fauser BC . Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril. 2011 Nov;96(5):1175–1189.
  • Barra F , Scala C , Mais V , et al. Investigational drugs for the treatment of endometriosis, an update on recent developments. Expert Opin Investig Drugs. 2018 May;27(5):445–458..
  • Surrey ES , Soliman AM , Palac HL , et al. Impact of elagolix on workplace and household productivity among women with moderate to severe pain associated with endometriosis: a pooled analysis of two phase III trials. The Patient - Patient-Centered Outcomes Research. 2019 Dec;12(6):651–660..
  • Pokrzywinski RM , Soliman AM , Chen J , et al. Achieving clinically meaningful response in endometriosis pain symptoms is associated with improvements in health-related quality of life and work productivity: analysis of 2 phase III clinical trials. Am J Obstet Gynecol. 2019 Nov 21. DOI:10.1016/j.ajog.2019.11.1255.
  • Vercellini P , Vigano P , Barbara G , et al. Elagolix for endometriosis: all that glitters is not gold. Hum Reprod. 2019 Feb 1;34(2):193–199.
  • Barra F , Seca M , Della Corte L , et al. Relugolix for the treatment of uterine fibroids. Drugs Today (Barc). 2019 Aug;55(8):503–512..
  • ClinicalTrials.gov . Efficacy and safety of OBE2109 in subjects with heavy menstrual bleeding associated with uterine fibroids (PRIMROSE 2). (NCT number): NCT03070951. [cited 2020 Apr 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03070951
  • ClinicalTrials.gov . Efficacy and safety of OBE2109 in subjects with heavy menstrual bleeding associated with uterine fibroids (PRIMROSE 1). (NCT number): NCT03070899. [cited 2020 Apr 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03070899
  • AbbVie . AbbVie announces positive topline results from phase 3 study evaluating investigational elagolix in women with uterine fibroids. [cited 2020 Apr 1]. Available from: https://news.abbvie.com/news/abbvie-announces-positive-topline-results-from-phase-3-study-evaluating-investigational-elagolix-in-women-with-uterine-fibroids.htm

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.