In the LIBERTY 1 study, daily relugolix combination therapy led to a reduction in menstrual blood loss of 84.3% and improvements in pain and quality of life.
Ayman Al-Hendy, MD, PhD
Results from the LIBERTY 1 study of relugolix combination therapy for uterine fibroids have indicated that the treatment has a 73.4% response rate compared to 18.9% for placebo. The phase 3 study compared a daily relugolix combination therapy of relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg to placebo.
Additionally, several secondary endpoints were achieved, including a mean reduction in menstrual blood loss from baseline of 84.3% among the relugolix combination therapy group.
“These results highlight the potential of a once daily oral medicine to become an important option to help women with uterine fibroids manage symptoms without invasive procedures or major surgery such as hysterectomy,” said Ayman Al-Hendy, MD, PhD, Professor and Director, Translational Research, University of Illinois College of Medicine.
Al-Hendy added that patients with uterine fibroids currently have a narrow array of treatment options for a condition that “can significantly decrease their quality of life.”
The LIBERTY 1 study enrolled 388 women with uterine fibroids and heavy menstrual bleeding—defined as menstrual blood loss volume of at least 80 mL in 2 consecutive cycles or 160 mL in a single cycle. Participants were randomized 1:1:1 to a daily relugolix combination therapy for 24 weeks, relugolix 40 mg daily monotherapy for 12 weeks followed by daily relugolix combination therapy for another 12 weeks, or daily placebo for 24 weeks.
The primary endpoint was defined as a menstrual blood loss volume of less than 80 mL and a ≥50% reduction in menstrual blood loss volume from baseline during the last 35 days of the 24-week trial. In the relugolix combination therapy group, 73.4% were responders, compared to 18.9% in the placebo group (P <.0001).
The relugolix combination therapy group and placebo group had comparable bone mineral density. Additionally, the distribution of change in bone mineral density at 24 weeks was similar for the 2 groups.
“We are incredibly pleased with the positive results of this first phase 3 study demonstrating a clinically meaningful response in a high proportion of women while maintaining bone health,” said Lynn Seely, MD, President and Chief Executive Officer of Myovant. “The improvements in symptoms most relevant to women, such as reduction in menstrual blood loss and pain, and improvement in quality of life are particularly exciting.”
Patients in the relugolix combination therapy group experienced a mean 84.3% reduction in menstrual blood loss from baseline (P <.0001). Myovant did not provide specifics, but reported that other secondary endpoints were met, including reduction in pain in women with pain at baseline (P <.0001), improvement in quality of life (P <.0001), amenorrhea defined as no or negligible blood loss, improvement in anemia in those women with anemia at baseline, and reduction in uterine volume.
Overall rates of adverse events were 62% and 66% for the relugolix combination and placebo groups, and they led to 5% and 4% discontinuation rates in those groups, respectively. Hot flush occurred in 11% and 8% of the relugolix combination and placebo groups and was the only adverse event that occurred at ≥10% in the treatment group and more frequently than in with placebo.
Data for the monotherapy plus combination therapy group were not provided in the company statement, and a request for details was not answered at the time of publication.
A replicate study, LIBERTY 2, enrolled 382 participants. Myovant expects results from the LIBERTY 2 study in the third quarter of 2019, and with positive results, will submit a New Drug Application (NDA) to the US Food and Drug Administration (FDA) by the end of 2019.