Relugolix

Relugolix is a small molecule, gonadotropin-releasing hormone (GnRH) receptor antagonist, and an oral investigational drug candidate for the treatment of uterine fibroids, endometriosis, and advanced prostate cancer.

More than 2,150 study participants have received treatment with relugolix in Phase 1, Phase 2, and Phase 3 clinical trials. Takeda has obtained marketing authorization in Japan for Relumina® (relugolix 40 mg tablets).

Relugolix is not approved by the FDA

How it works

As a GnRH receptor antagonist, relugolix binds to and blocks the GnRH receptor (GnRHR) in the anterior pituitary gland.

Blocking GnRH receptors decreases the release of gonadotropins – luteinizing hormone (LH) and follicle-stimulating hormone (FSH) – thereby decreasing the downstream production of estrogen and progesterone by the ovaries in women and testosterone by the testes in men.

Combination Therapy Approach for Women’s Health

We are developing relugolix 40 mg in combination with estradiol (1.0 mg) and a progestin (0.5 mg norethindrone acetate). Estradiol and progestins are hormones similar to those naturally-occurring in the body. Low-estrogen levels can weaken bone health and cause unwanted side effects such as hot flushes. Low doses of estradiol and progestins help offset these effects. We are investigating whether this combination optimizes estrogen levels to balance the potential benefits of relugolix, while maintaining bone health and mitigating side effects from a low-estrogen state.

Monotherapy Approach for Prostate Cancer

We are developing relugolix 120 mg following a single 360 mg loading dose. We are investigating whether this monotherapy decreases testosterone to low levels.

Clinical Trial Results

Relugolix is not approved by the FDA.

Uterine fibroids

In May 2019, we reported positive top-line results from the LIBERTY 1 trial to evaluate the efficacy and safety of relugolix combination therapy in 388 women with heavy menstrual bleeding associated with uterine fibroids. Relugolix combination achieved a 73.4% responder rate compared with 18.9% in the placebo group at 24 weeks, meeting the primary endpoint (p <0.0001). A responder was defined as the proportion of women who had a menstrual blood loss of less than 80 mL and at least a 50% reduction in menstrual blood loss from baseline during the last cycle as assessed by the alkaline hematin method. Six key secondary endpoints were also achieved, including reductions in menstrual blood loss and pain in addition to improvements in quality of life and anemia in those women with anemia at baseline. On average, women had an 84.3% reduction in menstrual blood loss compared to baseline. The mean percent change in bone mineral density was comparable between relugolix combination and placebo at 24 weeks. In October 2017, Takeda also reported positive top-line results from its Phase 3 trial in Japan of relugolix alone in 280 women with heavy menstrual bleeding associated with uterine fibroids. Relugolix achieved a responder rate that was non-inferior to leuprorelin, a GnRH agonist, also known as leuprolide acetate, thus meeting the primary endpoint of the study. In November 2017, Takeda also reported positive top-line results from its Phase 3 trial in Japan of relugolix in 65 women for the treatment of pain associated with uterine fibroids compared to placebo. Relugolix demonstrated a statistically significant improvement in pain in 57.6% of women compared to 3.1% of women receiving placebo. Adverse events in all these studies were consistent with the mechanism of action.

Endometriosis

In a double-blind, placebo-controlled Phase 2 trial in 487 patients with endometriosis, women who received relugolix experienced statistically significant, dose-dependent reductions in non-menstrual and menstrual pelvic pain. Adverse events were consistent with the mechanism of action.

Prostate cancer

In two randomized Phase 2 trials in approximately 228 men with advanced prostate cancer, relugolix suppressed testosterone to castrate levels and decreased prostate-specific antigen (PSA) in >90% of men at six months. Upon treatment discontinuation of relugolix, testosterone levels rose above castrate levels within days. Adverse events in both studies were consistent with the mechanism of action.

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