LIBERTY: LONG-TERM EXTENSION STUDY DEMONSTRATING ONE-YEAR EFFICACY AND SAFETY OF RELUGOLIX COMBINATION THERAPY IN WOMEN WITH SYMPTOMATIC UTERINE FIBROIDS

In the LIBERTY 1 and 2 trials, once-daily relugolix combination therapy (Rel-CT) reduced menstrual blood loss (MBL) volume and pain in women with uterine fibroids (UF) and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks (Al Hendy, ASRM 2019). Here we report on the long-term efficacy and safety of Rel-CT for up to 52 weeks of treatment. Multinational, Phase 3, open-label, long-term extension trial. Women with UF-associated heavy menstrual bleeding (HMB) who completed the 24-week, double-blind, placebo-controlled LIBERTY 1 and 2 trials were eligible to enroll in a 28-week extension study. All received once-daily Rel-CT (40 mg relugolix, an oral gonadotropin-releasing hormone receptor antagonist, estradiol 1 mg, norethindrone acetate 0.5 mg). The primary efficacy endpoint was the proportion of women who achieved or maintained an MBL volume < 80 mL and a ≥ 50% reduction from parent study baseline to the last 35 days of treatment, as measured by the alkaline hematin method. Secondary endpoints included mean % MBL reduction, amenorrhea rate, and improvements in anemia. Adverse events (AEs) and BMD changes by dual-energy X-ray absorptiometry were assessed. Outcomes were analyzed by treatment assignment: Rel-CT, delayed Rel-CT (relugolix 40 mg alone for 12 weeks, then Rel-CT for 12 weeks), and placebo, and were reported using descriptive statistics without statistical comparisons between groups. The Rel-CT group has the longest treatment duration (52 weeks): the other groups, where patients transitioned to Rel-CT, are supportive. Of the 770 randomized LIBERTY patients, 610 completed the primary study; 477 (78%) enrolled in the long-term extension and 363 (76%) completed it. The Rel-CT group demonstrated sustained improvement in HMB through 52 weeks with 87.7% of patients meeting the definition of responder. The mean MBL volume reduction from baseline was 89.9% with most patients (70.6%) achieving amenorrhea. The reductions in MBL led to substantial improvements (> 2 g/dL) in hemoglobin concentrations at Week 52 for most (59.0%) patients with anemia (< 10.5 g/dL) at baseline. Reductions in uterine and UF volume at Week 24 were sustained through Week 52. Consistent with the change observed at Week 24, the Bleeding Pain and Discomfort scale score was reduced by 51.3 points from baseline to Week 52, indicating that reduction in measures of symptom-associated distress were substantial and sustained. There was no disproportionate increase in the incidence of either serious or nonserious AEs in the Rel-CT group through the 52 weeks. The most frequently reported AEs were headache and hot flush. BMD was preserved with a mean % reduction of –0.80% (95% confidence interval: –1.36, –0.25) for lumbar spine BMD at Week 52. Efficacy and safety outcomes for delayed Rel-CT and placebo were consistent. Rel-CT showed durability of effect for both HMB and pain through 52 weeks of treatment in women with UF. No new safety concerns were identified, and bone mass was maintained.