Linzagolix: First Approval

Drugs - Tập 82 - Trang 1317-1325 - 2022
Susan J. Keam1
1Springer Nature, Auckland, New Zealand

Tóm tắt

Linzagolix (Yselty®) is an orally administered, selective, non-peptide small molecule gonadotrophin releasing hormone (GnRH) receptor antagonist that is being developed by Kissei Pharmaceutical for the treatment of uterine fibroids and endometriosis in women of reproductive age. Linzagolix binds to and blocks the GnRH receptor in the pituitary gland, modulating the hypothalamic pituitary-gonadal axis and dose-dependently reducing serum luteinising hormone and follicle-stimulating hormone production and serum estradiol levels. In June 2022, linzagolix was approved for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age in the EU. Linzagolix is under regulatory review the USA for this indication and is in phase 3 clinical development in the treatment of pain associated with endometriosis. This article summarizes the milestones in the development of linzagolix leading to this first approval for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age.

Tài liệu tham khảo

Dolmans MM, Cacciottola L, Donnez J. Conservative management of uterine fibroid-related heavy menstrual bleeding and infertility: time for a deeper mechanistic understanding and an individualized approach. J Clin Med. 2021;10(19):4389. Donnez J, Dolmans MM. Endometriosis and medical therapy-from progestogens to progesterone resistance to GNRH antagonists: a review. J Clin Med. 2021;10(5):1–21. Saunders PTK, Horne AW. Endometriosis: etiology, pathobiology, and therapeutic prospects. Cell. 2021;184(11):2807–24. Stewart EA, Cookson CL, Gandolfo RA, et al. Epidemiology of uterine fibroids: a systematic review. BJOG. 2017;124(10):1501–12. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244–56. Donnez J, Dolmans MM. GnRH antagonists with or without add-back therapy: a new alternative in the management of endometriosis? Int J Mol Sci. 2021;22(21):11342. Donnez J, Stratopoulou CA, Dolmans MM. Uterine adenomyosis: from disease pathogenesis to a new medical approach using GnRH antagonists. Int J Environ Res Public Health. 2021;18:9941. Vannuccini S, Petraglia F. Recent advances in understanding and managing adenomyosis. F1000Res. 2019;2019:8. Donnez J, Donnez O, Tourniaire J, et al. Uterine adenomyosis treated by linzagolix, an oral gonadotropin-releasing hormone receptor antagonist: a pilot study with a new “hit hard first and then maintain” regimen of administration. J Clin Med. 2021;10:5794. ObsEva. ObsEva provides update on Yselty® (linzagolix) clinical development program [media release]. 11 Jan 2021. http://www.obseva.com. Theramex. Theramex announces European Commission marketing authorization for Yselty® (linzagolix), an oral GnRH antagonist, for the treatment of symptoms of uterine fibroids [media release]. 11 Jun 2022. https://www.theramex.com/. European Medicines Agency. Linzagolix: EU summary of product characteristics. 2022. https://ec.europa.eu/health/documents/community-register/html/h1606.htm. Accessed 21 Jun 2022 ObsEva. ObsEva enters into licensing agreement with Theramex for the commercialization of linzagolix [media release]. 10 Feb 2022. https://www.obseva.com/. ObsEva. ObsEva presents clinical data on open-label pilot study of Yselty® (linzagolix) for the treatment of severe adenomyosis at ESHRE Virtual 37th Annual Meeting [media release]. 30 Jun 2021. http://www.obseva.com. ObsEva. ObsEva announces corporate updates [media release]. 27 Jul 2022. https://www.obseva.com/ ObsEva. ObsEva announces relationship with Syneos Health to commercialize linzagolix [media release]. 13 Oct 2021. https://www.obseva.com/. Kissei Pharmaceutical. Kissei announces licensing agreement with ObsEva SA for KLH-2109, a novel investigational drug for the treatment of endometriosis [media release]. 20 Nov 2015. http://www.kissei.co.jp. ObsEva. ObsEva and Kissei Pharmaceutical announce global agreement to develop and commercialize KLH-2109 for the treatment of endometriosis [media release]. 20 Nov 2015. http://www.obseva.com. Kissei Pharmaceutical. Licensing agreement for GnRH antagonist linzagolix with Bio Genuine in China [media release]. 2 Sep 2021. http://www.kissei.co.jp. ObsEva. Annual report 2020. 2021. https://www.obseva.com/wp-content/uploads/2021/02/Annual-Report-2020.pdf. Accessed 28 Feb 2022. ObsEva. Form F-1 registration statement. 2016. https://obsevasa.gcs-web.com/static-files/fb8b7386-97db-4b57-838b-4c3bea7ce980. Accessed 28 Feb 2022. Pohl O, Marchand L, Fawkes N, et al. Gonadotropin-releasing hormone receptor antagonist mono- and combination therapy with estradiol/norethindrone acetate add-back: pharmacodynamics and safety of OBE2109. J Clin Endocrinol Metab. 2018;103(2):497–504. Coss D. Regulation of reproduction via tight control of gonadotropin hormone levels. Mol Cell Endocrinol. 2018;463:116–30. Tezuka M, Tamai Y, Kuramochi Y, et al. Pharmacological characterization of linzagolix, a novel, orally active, non-peptide antagonist of gonadotropin-releasing hormone receptors. Clin Exp Pharmacol Physiol. 2022. https://doi.org/10.1111/1440-1681.13688. Taylor H, Donnez J, Bestel E, et al. Post-treatment efficacy and safety follow-up in women with uterine fibroids treated for 52 weeks with linzagolix [abstract no. A108]. Obstet Gynaecol. 2022;139:31S-S32. Pohl O, Baron K, Riggs M, et al. A model-based analysis to guide gonadotropin-releasing hormone receptor antagonist use for management of endometriosis. Br J Clin Pharmacol. 2021. https://doi.org/10.1111/bcp.15171. ObsEva. Company corporate presentation. 2022. https://www.obseva.com/wp-content/uploads/2021/02/ObsEva_Corporate-Deck_Latest.pdf. Accessed 1 Mar 2022. Bestel E, Gotteland JP, Donnez J, et al. Quality of life results after 52 weeks of treatment with linzagolix for endometriosis-associated pain [abstract no. 30B]. Obstet Gynecol 2020;135(Suppl 1):26S–7S. Bradley LD, Marsh EE, Garner E. Linzagolix may address the long-term treatment needs of women with uterine fibroids (uf) who have contraindications to hormonal add-back therapy (abt): results from two phase 3 randomized clinical trials [abstract no. P-931]. Fertil Steril. 2020;114(3 Suppl):e527. Stewart EA, Taylor HS, Taylor RN, et al. Efficacy and safety of linzagolix (lgx) for the treatment of heavy menstrual bleeding (hmb) due to uterine fibroids (uf): results from two phase 3 randomized clinical trials [abstract no. P-930]. Fertil Steril. 2020;114(3 Suppl):e527. Taylor H, Donnez J, Petraglia F, et al. Long term secondary efficacy of linzagolix for heavy menstrual bleeding (HMB) due to uterine fibroids (UF): 52-week results from two placebo-controlled, randomized, phase 3 trials [abstract no. O-135]. Hum Reprod. 2021;36(Suppl 1). ObsEva. Q3 report 2021. 2021. https://www.obseva.com/wp-content/uploads/2021/11/ObsEva-Q3-2021-Report.pdf. Accessed 28 Feb 2022. ObsEva. ObsEva announces positive topline results for linzagolix 200 mg with add-back therapy in the phase 3 EDELWEISS 3 trial in patients with moderate-to-severe endometriosis-associated pain [media release]. 6 Jan 2022. https://www.obseva.com/. ObsEva. ObsEva announces additional efficacy results for linzagolix 200 mg with add-back therapy (ABT) and linzagolix 75 mg without ABT in the phase 3 EDELWEISS 3 trial in patients with moderate-to-severe endometriosis-associated pain [media release]. 22 Mar 2022. https://www.obseva.com/. Donnez J, Taylor HS, Taylor RN, et al. Treatment of endometriosis-associated pain with linzagolix, an oral gonadotropin-releasing hormone-antagonist: a randomized clinical trial. Fertil Steril. 2020;114(1):44–55. Taylor RN, Bestel E, Gotteland JP, et al. Long term treatment of endometriosis associated pain (EAP) with linzagolix: efficacy and safety after 12 months of treatment [abstract no. P-539]. Fertil Steril. 2019;112(3 Suppl):e323. Kissei Pharmaceutical. R&D pipeline (out-licensing). 2022. https://www.kissei.co.jp/e_contents/rd/pipeline/. Accessed 1 Mar 2022.