Long-term Relugolix Combination Therapy for Symptomatic Uterine Leiomyomas

Abstract

Objective: In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.

Methods: Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders ). Analyses were conducted for all three randomized treatment groups from pivotal studies.

Results: Overall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma-associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.

Conclusion: Improvements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma-associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.

Clinical trial registration: ClinicalTrials.gov , NCT03049735; NCT03103087; NCT03412890.

Funding source: Myovant Sciences GmbH.

Fig. 1.. A. Primary efficacy analysis results: menstrual blood loss responder rate. Treatment responder: proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction from pivotal study baseline to the last 35 days of treatment in menstrual blood loss volume. B. Proportion of patients with menstrual blood loss volume less than 80 mL over the last 35 days of treatment. C. Patients with menstrual blood loss reduction of 50% or greater. Error bars represent 95% CIs. Data shown by randomization treatment assignment.

Fig. 2.. Least squares percent change in menstrual blood loss volume from baseline to week 52. Error bars show 95% CIs.

Fig. 3.. A. Proportion of responders* among patients with anemia at baseline. Anemia-evaluable population: patients with hemoglobin concentration of 10.5 g/dL or less at baseline and with a hemoglobin value at week 24. *Treatment responder (hemoglobin): proportion of women with hemoglobin concentrations of 10.5 g/dL or less at pivotal study baseline who achieved an increase of more than 2 g/dL at week 52. Error bars show 95% CI. B. Least squares mean percent change in hemoglobin concentrations with relugolix combination therapy in women with anemia at baseline. Error bars show 95% CI.

Fig. 4.. Least squares mean change in total Health-Related Quality of Life (HRQOL) scores at week 24 and week 52 (A) and least squares mean change in HRQOL subscale scores from baseline to 52 weeks (B). Error bars show upper 95% CI.

Fig. 5.. Percent change in uterine leiomyoma volume (A) and uterine volume (B). Error bars show upper and lower 95% CI.

Fig. 6.. Percent change in lumbar spine bone mineral density (BMD) (A) and total hip BMD (B) to week 52. Error bars show 95% Cis.