Linzagolix is a new, investigational, non-peptide, GnRH receptor antagonist being developed to treat endometriosis-associated pain (EAP). The EDELWEISS trial was a Phase 2b, double-blind, randomized, placebo-controlled, multicenter, dose-ranging trial in USA and Europe evaluating once daily oral doses of 50, 75, 100 and 200 mg for up to 52 weeks. Subjects randomized to placebo were crossed over to 100 mg after 12 weeks and those randomized to 200 mg were crossed over to 100 mg after 24 weeks.
IRB approval was obtained. Participants were women with surgically confirmed endometriosis and moderate to severe EAP. Changes in serum lipids were assessed up to 52 weeks.
327 patients were randomized and treated. Mean age was 32 years and mean BMI was 26. There were small percentage increases in LDL-cholesterol (C), HDL-C, LDL-C/HDL-C ratio and triglycerides, which did not increase further at 24 and 52 weeks. Except for LDL-C/HDL-C ratio, the largest increases were observed in the linzagolix 200 mg dose group; at week 24 there was an approximately 8% increase in HDL-C, 10% increase in LDL-C and 24% increase in triglycerides. In all treatment groups, the percentage of women with LDL-C > 160 mg/dL or triglycerides > 200 mg/dL at 24 weeks less than 10% and overall the percentages were similar to baseline.
Linzagolix doses of 75 to 200 mg taken once daily for 52 weeks resulted in small percentage increases in serum lipids after 12 weeks, which did not increase further after 52 weeks of treatment.