O-269 Long term efficacy of Linzagolix in women with endometriosis-associated pain

Abstract Study question Does once-daily linzagolix taken up to 12 months maintain pain reduction observed at 6 months in women with endometriosis? Summary answer Linzagolix alone or in combination with combined add-back therapy (ABT) for 12 months maintains improvements of endometriosis-associated pain (EAP) observed at 6 months. What is known already Linzagolix is an oral GnRH antagonist under development for EAP. In the EDELWEISS 3 study, the 200mg+ABT dose met its co-primary endpoints at 3 months by reducing dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) and secondary endpoints such as DYS, NMPP, overall pelvic pain and dyschezia as well as interference of pain with daily activities at 6 months. Linzagolix 75mg significantly reduced dysmenorrhea but not NMPP at 3 months. Both doses of linzagolix were well tolerated over 6 months of treatment. Study design, size, duration EDELWEISS 6 was the extension study of EDELWEISS 3, a placebo-controlled Phase 3 study, investigating linzagolix 75mg and 200mg+ABT for up to 6 months in women with moderate to severe EAP. Subjects who completed EDELWEISS3 were invited to enter the extension study for an additional 6-month treatment on the same linzagolix dose; placebo subjects were randomized to either active dose. After end of treatment, subjects entered a drug-free post-treatment period of 6 months. Participants/materials, setting, methods Women participating to EDELWEISS 6 received linzagolix for up to 12 months consecutively. Key efficacy assessments included dysmenorrhea and non-menstrual pelvic pain (NMPP), dyspareunia (assessed with a 4-point VRS), overall pelvic pain and dyschezia (assessed with an 11-point NRS), and interference of pain with daily activities (assessed with the EHP-30 pain domain) at Month 12. We report the results for dysmenorrhea and NMPP. Main results and the role of chance Of 484 participants in EDELWEISS 3, 353 (72.9%) entered EDELWEISS 6 and were evaluated for efficacy. Demographics were similar to EDELWEISS 3 with a mean age of 35 years, a BMI of 24kg/m2 and 99% of subjects being White. Mean (SD) monthly baseline dysmenorrhea and NMPP pain scores on the VRS were 2.28 (0.41) and 1.76 (0.45), respectively. The threshold for a meaningful pain reduction was established at Month 3, being -1.10 and -0.80 for dysmenorrhea and NMPP, respectively. At Month 3, the proportion of subjects with a reduction of dysmenorrhea of 1.10 or greater, and stable or decreased use of analgesics was 45.2% for the 75mg group and 75.4% for the 200mg+ABT group, which increased to 49.6% and 84.7%, respectively, at Month 6, the end of EDELWEISS 3. At Month 12, the end of EDELWEISS 6 treatment, the proportion of subjects was further increased to 55.9% and 91.0%, respectively. For NMPP, the proportion of subjects with a reduction of 0.80 or greater and stable or decreased use of analgesics at Month 3 was 36.5% for 75 mg and 51.7% for 200mg+ABT, increased to 54% and 61% at Month 6, and increased to 59.5% and 67.6%, respectively, until Month 12. Limitations, reasons for caution Edelweiss 6 is the extension of the previously reported double blind, placebo controlled Edelweiss 3 study. The results confirm efficacy of 200mg + ABT at 12 months. Longer term data is required to further understand efficacy of GnRH antagonists in women with endometriosis associated pain. Wider implications of the findings The linzagolix 200mg+ABT group provided substantial and sustained improvement in EAP symptoms. The 75mg which did not meet the primary endpoint in EDELWEISS 3 still demonstrated marked improvements. There exists a substantial need for different treatment regimens in women suffering from endometriosis. Trial registration number NCT04335591