Relugolix for treating uterine fibroids

The study in the journal BMC Women’s Health was conducted at 36 sites in Japan among 216 women with uterine leiomyomas and heavy menstrual bleeding, defined as a pictorial blood loss assessment chart (PBAC) score of greater than or equal to 120 in 1 menstrual cycle.¹

From November 2011 to September 2012, patients were randomized 1:1:1:1 to relugolix 10 mg, 20 mg, 40 mg, and placebo, orally once daily for 12 weeks.

The mean age of patients ranged in age from 41 to 43 years across the 4 treatment groups. There were also no apparent differences among the groups for uterine or myoma volumes.

Overall, 99.1% (n = 214) of patients were fully analyzed.

The chief endpoint was the proportion of patients with a total PBAC score of less than 10 from week 6 to 12.

The proportion (difference vs placebo) of patients that achieved the primary endpoint in the placebo and 10 mg, 20 –mg, and 40 mg relugolix groups were ; 20.8% (P < 0.001); 42.6% (P < 0.001); and 83.3% (P < 0.001), respectively.

Among secondary endpoints, PBAC scores of less than 10 for weeks 2 through 6 and weeks 2 through 12 were similar to the primary endpoint results.

Some patients also achieved amenorrhea at weeks 6 to 12 of the study, with the highest proportion in the relugolix 40 mg group, whereas there was no amenorrhea in the placebo group. Comparable results were observed for the proportion of patients who attained amenorrhea at weeks 2 to 6.

Mean myoma and uterine volumes increased during the study in the placebo group, while the volumes in all relugolix groups decreased from week 2 and continued to decrease during weeks 4, 8, and 12, with the largest decrease in volumes in the relugolix 40 mg group.

At week 12, uterine and myoma volumes were reduced by approximately 40% in the relugolix 40 mg group vs an increase of 10% in the placebo group.

Furthermore, hemoglobin levels increased in the relugolix 20 and 40 mg groups. By week 12, the mean change in standard deviation (SD) from baseline in hemoglobin was 0.83 g/dL and 0.93 g/dL for the relugolix 20 and 40 mg groups, respectively, while only a 0.20 g/dL change in the placebo group.

The blood concentrations of hemoglobin also tended to improve with relugolix therapy, irrespective of the use of iron preparations.

Women in the relugolix 40 mg group with a pain severity of greater than or equal to 4 on the numerical rating scale (NRS) at baseline were significantly more likely to achieve no pain or minimal pain during the 28 days prior to the final dose of study medication, and reported a reduction in pain score of 50% or more, compared to the placebo group.

Treatment-emergent adverse events (TEAEs) with an incidence of at least 10% were nasopharyngitis, headache, metrorrhagia, menorrhagia, genital hemorrhage, hot flushes, and menstruation irregular.

TEAEs were comparable in the 20 mg and 40 mg groups but were more frequent than in the placebo group. Most adverse events were mild or moderate in intensity.

A decrease in bone mineral density (BMD) was observed from baseline to week 12 in all four groups, with mean SD percentage changes of − 0.75, − 1.93, and − 2.27 in the relugolix 10, 20, and 40 mg groups, respectively, compared with only − 0.24 in the placebo group.

Still, the menstrual cycle resumed in 98% of full evaluated patients.

Reference

1. Hiroshi H, Seki Y, Kusumoto T, et al. Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial. BMC Women’s Health. Published online October 28, 2011. doi:10.1186/s12905-021-01475-2