Linzagolix promising for endometriosis-associated pain
Once-daily treatment with linzagolix, a novel, oral GnRH* antagonist, with or without add-back therapy (ABT), reduces dysmenorrhoea and nonmenstrual pelvic pain (NMPP), among women with endometriosis, according to the EDELWEISS 3 trial presented at ESHRE 2023.
At 3 months, the percentage of responders, defined as women with a clinically meaningful reduction in dysmenorrhoea and NMPP, was significantly higher in the linzagolix 200 mg + ABT group vs the placebo group (72.9 percent vs 23.5 percent; p<0.001 and 47.3 percent vs 30.9 percent; p=0.007, respectively).
A similar responder rate for dysmenorrhoea was also observed among those who received linzagolix 75 mg alone compared with those on placebo (44.0 percent vs 23.5 percent; p<0.001). However, the responder rate for NMPP was not significantly different between the treatment groups (38.9 percent vs 30.9 percent; p=0.279).
“At 3 months, linzagolix 200 mg + ABT met the co-primary objectives of reduction in dysmenorrhoea and NMPP, whereas linzagolix 75 mg alone significantly improved dysmenorrhoea but not NMPP, said lead author Professor Marie-Madeleine Dolmans from the Université Catholique de Louvain in Brussels, Belgium. [ESHRE 2023, abstract O-027]
This phase III, double-blind, placebo-controlled trial analysed 484 women (mean age 34.9 years) with moderate-to-severe endometriosis-associated pain who were randomized to receive linzagolix 200 mg + ABT (oestradiol 1 mg/0.5 mg norethisterone acetate), linzagolix 75 mg alone, or placebo for 6 months.
By 6 months, a significant decrease in pain score for dysmenorrhoea and NMPP was observed with linzagolix 200 mg + ABT than with placebo (least squares [LS] mean change from baseline, -1.83 vs -0.66; p<0.001 and -0.92 vs -0.66; p=0.002, respectively) as assessed by a 4-point verbal rating scale (VRS).
Similarly, those on linzagolix 75 mg monotherapy achieved significant improvements in VRS scores for dysmenorrhoea (LS mean change from baseline, -1.10 vs -0.66; p< 0.001) and NMPP (LS mean change from baseline, -0.84 vs -0.66; p=0.048) compared with those on placebo at 6 months.
As assessed on an 11-point numeric rating scale (NRS), patients treated with either linzagolix 200 mg + ABT or linzagolix 75 mg alone achieved a 2.0-point reduction in NRS score for dyschezia from baseline to month 6 compared with a 1.4-point reduction among those on placebo (p=0.012 and p=0.015, respectively).
The NRS score for overall pelvic pain was also significantly improved in the linzagolix groups vs the placebo group (LS mean change from baseline, -3.4; p<0.001 [200 mg + ABT] and -2.8; p=0.024 [75 mg] vs -2.2).
The linzagolix groups also reported less pain interference with daily activities, as indicated by an EHP-30** score of -35.6 (p<0.001) for 200 mg + ABT and -27.4 (p=0.001) for 75 mg alone vs -19.5 for the placebo group.
Hot flashes, headache, and fatigue were the most commonly reported adverse events for all the treatment groups. Linzagolix doses were well tolerated, Dolmans said.
“Overall, the linzagolix 200 mg + ABT regimen provided substantial improvement in endometriosis-associated pain. Although the 75 mg dose was less effective, it still demonstrated marked improvements in pain,” said the researchers.
Both linzagolix 75 mg monotherapy and linzagolix 200 mg + ABT improved dysmenorrhoea and NMPP, dyschezia, and overall pelvic pain, Dolmans emphasized.Linzagolix [100 or 200 mg with or without ABT] is approved in Europe and the UK for the treatment of moderate-to-severe symptoms of uterine fibroids, but remains investigational for endometriosis-associated pain.