Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3)

• DOI: 10.1093/humrep/deae076
• Publication Date: 2024-04-22T23:15:32Z
• Authors: Jacques Donnez; Christian Becker; Hugh Taylor; Francisco Carmona...; Olivier Donnez; Andrew Horne; Maciej Paszkowski; Felice Petraglia; Stefan P Renner; Amisha Patel; Mitra Boolell; Elke Bestel; Marie-Madeleine D...
• Keywords: Norethisterone acetate; Norethisterone

Abstract STUDY QUESTION Does linzagolix administered orally once daily for up to 3 months at a dose of 75 mg alone or 200 in combination with add-back therapy (ABT) (1.0 estradiol; 0.5 norethindrone acetate, also known as norethisterone acetate [NETA]) demonstrate better efficacy than placebo the management endometriosis-related dysmenorrhea and non-menstrual pelvic pain? SUMMARY ANSWER Combining ABT was found significantly reduce pain therapy, while yielded significant decrease only months. WHAT IS KNOWN ALREADY? A previously published Phase 2, dose-finding study reported that daily, promotes full suppression estradiol secretion serum levels below 20 pg/ml noted addition may be needed manage hypoestrogenic side effects. At lower doses (75 100 mg/day), maintains values within target range 20–60 pg/ml, which could ideal alleviate symptoms linked endometriosis. DESIGN, SIZE, DURATION EDELWEISS multicenter, prospective, randomized, placebo-controlled, double-blind, double-dummy evaluate safety treatment moderate-to-severe endometriosis-associated pain. Treatment 6 PARTICIPANTS/MATERIALS, SETTING, METHODS In trial, 486 subjects were randomized 1:1:1 ratio one three groups: placebo, association ABT. Pain measured on verbal rating scale recorded an electronic diary. MAIN RESULTS AND THE ROLE OF CHANCE months, met primary objective, showing clinically meaningful statistically reductions pain, stable decreased use analgesics. The proportion responders group 72.9% compared 23.5% (P < 0.001), rates 47.3% 30.9% = 0.007), respectively. demonstrated reduction versus 44.0% 0.001). Although showed trend toward relative it not 0.279). Significant improvements dyschezia overall observed both groups when placebo. Small dyspareunia scores but they significant. groups, effects mild, low hot flushes bone density loss <1%. therapy. LIMITATIONS, REASONS FOR CAUTION Efficacy between placebo; however, would useful have results from comparative studies estro-progestogens progestogens. It will important ascertain whether gonadotropin-releasing hormone antagonists benefits over traditional first-line medications. WIDER IMPLICATIONS FINDINGS Linzagolix quality life improved risks vasomotor minimized due suitable chronic without need concomitant hormonal ABT, further research is confirm this. If confirmed, offer viable option women who do want wish whom contraindicated. FUNDING/COMPETING INTEREST(S) Funding provided by ObsEva (Geneva, Switzerland). Analysis data manuscript writing partially supported Switzerland), Theramex (London, UK) Kissei (Japan) grant 5/4/150/5 awarded M.-M.D. FNRS. J.D. member scientific advisory board until August 2022, PregLem, received personal fees Gedeon Richter, Theramex. consulting fees, speakers’ travel support Obseva Theramex, paid their institution. C.B. has Myovant, Richter—all funds went University Oxford. He monitoring supervising current study, served endometriosis Myovant. H.T. grants Abbvie past president ASRM. F.C.H. Richter O.D. lectures clinical Preglem independent study. A.H. NIHR, UKRI, CSO, Wellbeing Women, Roche Diagnostics; he A.H.’s institution honoraria consultancy Diagnostics, Gesynta, Joii. M.P. nothing declare. F.P. S.P.R. been Richter. A.P. M.B. are employees E.B. employee ObsEva, sponsor chair working consultant since December 2022; she owns stock options ObsEva. TRIAL REGISTRATION NUMBER NCT 03992846. DATE June 2019. FIRST PATIENT’S ENROLLMENT 13