Drug Design, Development and Therapy (Feb 2023)
Profile of Linzagolix in the Management of Endometriosis, Including Design, Development and Potential Place in Therapy: A Narrative Review
Abstract
Jacques Donnez,1,2 Luciana Cacciottola,3 Jean-Luc Squifflet,4 Marie-Madeleine Dolmans3,4 1Department of Gynaecology, Université Catholique de Louvain, Brussels, Belgium; 2Société de Recherche pour l’Infertilité (SRI), Brussels, Belgium; 3Gynecology Research Laboratory, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; 4Gynecology Department, Cliniques Universitaires St-Luc, Brussels, BelgiumCorrespondence: Marie-Madeleine Dolmans, Gynecology Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Mounier 52, bte B1.52.02, Brussels, 1200, Belgium, Tel +32 02 764 5237, Fax +32 02 764 9507, Email [email protected]: Estrogens play a critical role in the pathogenesis of endometriosis and it is logical to assume that lowering estradiol levels with oral gonadotropin-releasing hormone (GnRH) antagonists may prove effective, especially in women who fail to respond to progestogens. Indeed, due to progesterone resistance, oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis, but are ineffective in 33% of women. Oral GnRH antagonists have therefore been evaluated for management of premenopausal women with endometriosis-associated pelvic pain. The first publication on these drugs reported the efficacy of elagolix. The present paper is a narrative review of linzagolix, which is an orally administered GnRH receptor antagonist with low pharmacokinetic/pharmacodynamic variability. It binds to and blocks the GnRH receptor in the pituitary gland, resulting in a dose-dependent drop in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production. This reduction in LH and FSH levels in turn leads to a dose-dependent decline in estrogen. Phase 2 and 3 trials are reviewed and discussed here. There is a place for GnRH antagonists in the management of symptomatic endometriosis, and linzagolix with or without add-back therapy (ABT) is one option that can be used at low doses, avoiding the need for ABT, which is contraindicated in some patients.Keywords: endometriosis, pelvic pain, dysmenorrhea, progesterone resistance, GnRH antagonist
