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Combination therapy with relugolix (Orgovyx) relieved heavy bleeding and pain associated with uterine fibroids, without significantly increasing the risk of hypoestrogenic side effects, researchers reported in a pair of phase III clinical trials.

In the two LIBERTY trials, 71% and 73% of patients, respectively, who received relugolix -- an oral gonadotropin-releasing hormone (GnRH) receptor antagonist -- along with estradiol and norethindrone acetate experienced significant reductions in blood loss, compared with 19% and 15% of those in a placebo-only group, reported Ayman Al-Hendy, MD, PhD, of the University of Chicago Medicine, and colleagues.

Patients who received the combination therapy also had improvements in pain, distress from bleeding and pelvic discomfort, anemia, and experienced reduced uterine volume. However, the investigators did not observe significant shrinkage in fibroid volume, they reported in the .

Al-Hendy's group observed similar bone mineral density (BMD) measures in the placebo and relugolix combination therapy groups; but MD decreased among patients who received relugolix monotherapy.

Relugolix is currently .

"For the first time, we have an oral treatment that can effectively and safely improve the symptoms of uterine fibroids, particularly heavy menstrual bleeding," Al-Hendy said in an interview, adding that relugolix may be a viable, longer-term alternative to the current treatments available for fibroids patients.

One other oral therapy, Oriahnn (elagolix, estradiol, and norethindrone acetate), is FDA approved for fibroid-related bleeding. However, the drug can only be taken for up to 24 months due to the risk of bone loss.

"The goal of this program from the beginning was to develop an effective and long-term treatment as a viable alternative to hysterectomy," Al-Hendy stated. "Any patient with uterine fibroids would be a good candidate for this non-surgical treatment."

Lauren Schiff, MD, associate professor of minimally invasive gynecologic surgery at the school of medicine at the University of North Carolina at Chapel Hill, said that relugolix shapes up as an attractive non-surgical alternative for patients who suffer from fibroids. As these trials show a safe and effective option to reduce heavy bleeding and pain, the treatment may be ideal for premenopausal patients who do not want to pursue surgery, said Schiff, who was not involved in the study.

However, before relugolix could be considered for longer use, Schiff said understanding BMD past the 6-month mark is critical. "If the bone density safety measure is maintained for long-term use, then this would be really ideal medication," she told 番茄社区.

Uterine fibroids affect around 70% of white and 80% of Black people with a uterus, Al-Hendy and colleagues wrote. Approximately a quarter of those affected by fibroids have symptoms, which often include heavy menstrual bleeding and pain.

Injectable long-acting GnRH agonists are effective treatments for uterine fibroids, but are typically not recommended for long-term use because of their hypoestrogenic effects, including BMD loss. For example, Oriahnn, an elagolix combination therapy, is only eligible for use up to two years due to effects on BMD.

The LIBERTY trials were two identical, international studies that recruited participants from North America, South America, Africa, and Europe. Participants were randomized between 2017 and 2018.

Participants in the intervention group received relugolix combination therapy once daily for 6 months, which included 40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate. Two comparative groups were included in the trials: a placebo group and a delayed relugolix combination therapy group, who received monotherapy for the first 3 months and combination therapy for the remainder of the trial.

The primary endpoint of the trial was blood loss less than 80 ml, and more than a 50% reduction in total blood loss from the start of the trial. The investigators assessed several secondary outcomes, including amenorrhea, volume of menstrual blood loss, distress, pain, anemia, fibroid volume, and uterine volume.

Around 388 participants were randomized in the first trial, and 382 in the second. All trial participants were around age 42, and more than 50% in each comparative group were Black.

Around three-quarters of patients who received relugolix combination therapy reached the primary endpoint, with the treatment effects appearing similar regardless of race or other baseline characteristics.

Amenorrhea over the last 35 days of the trial occurred in 52% and 50% of participants who received relugolix combination therapy in each trial, respectively. Pain scores, which were measured by a bleeding and pelvic discomfort scale, were also improved in the relugolix combination groups.

The prevalence of side effects was similar in the relugolix combination therapy group and the placebo cohort, with hot flashes being the most commonly reported side effect in the trial.

Al-Hendy and colleagues recognized that many participants who self-reported pain and heavy menstrual bleeding were not eligible for this research due to strict assessment criteria, which may limit generalizability. Additionally, the trial duration was limited to 6 months. The investigators stated that they plan to release data from a 28-week extension study, along with a 52-week randomized-withdrawal trial, that may provide more information on long-term safety and efficacy.

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