Relugolix Confirmed to Cut Menstrual Bleed by Half in Most Women With Fibroids

By Gene Emery

February 18, 2021

(Reuters Health) - Daily relugolix therapy cuts menstrual bleeding by at least half without affecting bone density in 71% of women with uterine fibroids, according to results from the LIBERTY 2 trial, published by The New England Journal of Medicine.

The oral gonadotropin-releasing hormone (GnRH) receptor antagonist from Myovant Sciences, approved by the U.S. Food and Drug Administration last year as a treatment for advanced prostate cancer, is being reviewed by the FDA as a uterine fibroid therapy.

The newly-published findings, involving 382 women treated at 99 sites around the world, closely mirror the results from the LIBERTY 1 trial reported nearly two years ago. In that study, involving 388 women, 73% of the volunteers who received relugolix had a reduction in menstrual blood loss of at least 50% and a volume of less than 80 ml.

"For the first time we have a good, reliable, long-term treatment for fibroids as an alternative to surgery," chief author Dr. Ayman Al-Hendy told Reuters Health in a telephone interview. "I'm hoping this will make a dent in the number of hysterectomies."

Myovant paid for both studies. The company held and analyzed the data. Most women who received the drug got it in combination with 1 mg of estradiol and 0.5 mg of norethindrone acetate to mute the side effects of relugolix alone.

In October, the Al-Hendy team reported at a meeting of the American Society for Reproductive Medicine that a full year of treatment reduced mean menstrual blood volume by nearly 90%, with amenorrhea seen in more than two thirds of the women.

By age 50, an estimated 70% of white women and 80% of Black women have at least one fibroid. One quarter of the cases produce symptoms, typically heavy menstrual bleeding and sometimes pain. Fibroid treatment in the United States costs an estimated $34 billion per year.

Contraceptive therapy may provide temporary relief but "the vast majority of patients fail after three to six months," said Dr. Al-Hendy, vice chairman for research for the department of obstetrics and gynecology at the University of Chicago. Surgery is the only reliable alternative.

If the new treatment gets FDA approval, which could come sometime this summer based on data following volunteers for up to two years, women "will have a viable, non-surgical alternative" for fibroids, he said.

The LIBERTY studies were done on women aged 18 to 50. For 24 weeks, one third received placebo, another third took the relugolix combination therapy and the rest took relugolix alone for 12 weeks followed by the relugolix combination for another 12 weeks. The women were assessed every 4 weeks. Blood loss was measured during the final month of treatment.

In 71% of the relugolix recipients, menstrual blood loss was cut by at least half. A similar reduction was seen in only 15% of placebo patients (P<0.001). (In the LIBERTY 1 study, the rates were 73% and 19% respectively.) Race did not appear to affect the results.

The actual mean reduction in blood loss was 84% with the drug and 15% with placebo (P<0.001).

Amenorrhea was seen in 50% of women on the drug versus 3% on placebo.

In the six-month extension of the study, "the numbers just keep getting better," said Dr. Al-Hendy. "The reduction in the amount of menstrual blood loss went up close to 90% and amenorrhea went up to 65%. I'm very excited about this."

"Participants in our two trials described considerable discomfort and distress associated with their fibroids at baseline, with those in the relugolix combination therapy group reporting significantly less distress from bleeding, passing of blood clots, and tightness or pressure in the pelvic area at the end of the treatment period than those who received placebo," the researchers said.

The treatment did not produce a significant decrease in the volume of the largest fibroid, although overall uterine volume did decrease (P=0.008).

Pain and discomfort scores showed a significant reduction in 47.1% of women receiving relugolix combination therapy compared to 17.1% who received placebo.

Serious side effects were uncommon.

The most common side effect was hot flashes, which were seen in 4% of placebo recipients, 6% of those who got the relugolix combination, and 35% who initially got straight relugolix without the estradiol and norethindrone acetate.

Similarly, bone density declined in the women who received straight relugolix at first but the drop seemed a plateau when they were switched to the combination. Density declined to a lesser degree with the combination. It generally remained highest with placebo.

As 120 mg per day prostate cancer treatment, sold under the brand name Orgovyx, relugolix costs about $2,400 a month. The dose used in the LIBERTY studies is 40 mg.

SOURCE: The New England Journal of Medicine, online February 17, 2021.