Relugolix was approved for use for the treatment of uterine fibroids in Japan in January 2019, and for the treatment of prostate cancer in the United States in December 2020.[12][13]
Relugolix is approved in the United States for the treatment of prostate cancer in men and in Japan for the treatment of uterine fibroids (uterine leiomyoma) in women.[12][7][5]
A dosage of relugolix of 40 mg once per day has been found to suppress estradiol levels to postmenopausal levels (<20 pg/mL) within 24 hours in premenopausal women.[1] In the control group of women, estradiol levels fluctuated between 50 and 250 pg/mL.[1] Estradiol levels have been found to return to normal concentrations within 4 weeks of discontinuation of relugolix in premenopausal women.[1] The medication additionally suppresses levels of progesterone, luteinizing hormone, and follicle-stimulating hormone in premenopausal women.[1] Relugolix at a dosage of 40 mg or more once per day has been found to reduce testosterone levels to sustained castrate levels (<20 ng/dL) in men.[11] It additionally suppresses luteinizing hormone and follicle-stimulating hormone levels in men.[11]
A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL (47 nmol/L) after 1.5 hours.[1]Steady-state levels are reached within 7 days with 40 mg/day relugolix administration.[1] There is an approximate 2-fold accumulation of relugolix by 2 weeks of continuous administration.[1] Food diminishes the oral bioavailability of relugolix by about 50%.[1]
Relugolix was first described in 2004.[16][8] It superseded sufugolix (developmental code name TAK-013), which was developed by the same researchers.[8] Relugolix was approved for the treatment of uterine fibroids in Japan in January 2019.[12][13] It was the second orally active GnRH antagonist to be introduced for medical use, following elagolix (brand name Orilissa) in July 2018.[12][17] Relugolix was approved for the treatment of prostate cancer in the United States on 18 December 2020.[12][5]
The FDA approved relugolix based on evidence from a clinical trial (NCT03085095) of 930 participants 48 to 97 years old with advanced prostate cancer.[18] The trial was conducted at 155 sites in the United States, Canada, and countries in South America, Europe and the Asia Pacific region.[18] All participants in the trial had advanced prostate cancer.[18] Participants were randomly assigned to receive either one relugolix tablet daily (on the first day they received three tables) or an active control (leuprolide acetate) which was given as an injection under the skin every three months.[18] The participants and healthcare providers were aware of which treatment was being given.[18] The treatment lasted for 48 weeks.[18] The efficacy of relugolix was assessed by the percentage of participants who achieved and maintained low testosterone level equal to castration.[18]
Relugolix is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and JANTooltip Japanese Accepted Name.[19][20] It is also known by its former developmental code names RVT-601 and TAK-385.[12][19]
Relugolix is sold under the brand name Orgovyx for the treatment of prostate cancer and under the brand name Relumina for the treatment of uterine fibroids.[12][13][7][5] Relugolix compounded with ethinyl estradiol and norethindrone is sold under the brand name Myfembree for the treatment of uterine fibroids.[21]
In February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Orgovyx, intended for the treatment of prostate cancer.[22] The applicant for this medicinal product is Myovant Sciences Ireland Limited.[22] Relugolix was approved for medical use in the European Union in April 2022.[6][23]
^ ab"Orgovyx EPAR". European Medicines Agency. 22 February 2022. Retrieved 3 March 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ abcdeMiwa K, Hitaka T, Imada T, Sasaki S, Yoshimatsu M, Kusaka M, et al. (July 2011). "Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor". Journal of Medicinal Chemistry. 54 (14): 4998–5012. doi:10.1021/jm200216q. PMID21657270.
^ abcNakata D, Masaki T, Tanaka A, Yoshimatsu M, Akinaga Y, Asada M, et al. (January 2014). "Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice". European Journal of Pharmacology. 723: 167–174. doi:10.1016/j.ejphar.2013.12.001. PMID24333551.
^ abcStreuli I, de Ziegler D, Borghese B, Santulli P, Batteux F, Chapron C (March 2012). "New treatment strategies and emerging drugs in endometriosis". Expert Opinion on Emerging Drugs. 17: 83–104. doi:10.1517/14728214.2012.668885. PMID22439891. S2CID27472695.
^US 7300935, Cho N, Imada T, Hitaka T, Miwa K, Kusaka M, Suzuki N, "Thienopyrimidine compounds and use thereof", issued 27 November 2007, assigned to Takeda Pharmaceutical Co Ltd.
^ ab"Orgovyx: Pending EC decision". European Medicines Agency. 24 February 2022. Archived from the original on 27 February 2022. Retrieved 27 February 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^Goenka L, George M, Sen M (June 2017). "A peek into the drug development scenario of endometriosis - A systematic review". Biomedicine & Pharmacotherapy. 90: 575–585. doi:10.1016/j.biopha.2017.03.092. PMID28407578.
Elsharoud A, Ali M, Al-Hendy A (2019). "Relugolix. GnRH (LHRH) receptor antagonist, Treatment of uterine fibroids, Treatment of endometriosis-related pain, Treatment of prostate cancer". Drugs of the Future. 44 (2): 131. doi:10.1358/dof.2019.44.2.2927590. ISSN0377-8282. S2CID87369995.
Clinical trial number NCT03085095 for "A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer (HERO)" at ClinicalTrials.gov
This article incorporates text from this source, which is in the public domain.
