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 4,250 study participants have received treatment with relugolix in Phase 1, Phase 2, and Phase 3 clinical trials.

Relugolix is not approved by the FDA.

How it works

As a GnRH receptor antagonist, relugolix binds to and blocks the GnRH receptor 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.

Myovant Relugolix Combination Therapy Image

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 flashes. Low doses of estradiol and progestins help offset these effects. We are investigating whether this combination maintains estrogen in the low normal range to balance the potential benefits of relugolix, while also maintaining bone health and mitigating the side effects that can result from a low-estrogen state.

Myovant Relugolix Monotherapy Image

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

Our Phase 3 clinical program for uterine fibroids consisted of two multinational, replicate pivotal clinical studies (LIBERTY 1 and LIBERTY 2) of relugolix combination therapy (relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg) in women with heavy menstrual bleeding associated with uterine fibroids for 24 weeks. Eligible women who completed the LIBERTY 1 or LIBERTY 2 studies were offered the opportunity to enroll in an active treatment extension study in which all women received relugolix combination therapy for an additional 28-week period for a total treatment period of 52 weeks, designed to evaluate the safety and sustained efficacy of longer-term treatment. Upon completion of this 52-week total treatment period, eligible women could elect to participate in a second 52-week randomized withdrawal study designed to provide two-year safety and efficacy data on relugolix combination therapy and to evaluate the need for maintenance therapy. Across studies, a response was defined as a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction from baseline in menstrual blood loss volume during the last 35 days of treatment measured using the alkaline hematin method.

LIBERTY 1 and 2 met the primary endpoint (p < 0.0001) with 73.4% and 71.2% of women receiving relugolix combination therapy achieving the responder criteria compared with 18.9% and 14.7% of women receiving placebo at 24 weeks, respectively. On average, women receiving relugolix combination therapy in both studies experienced an 84.3% reduction in menstrual blood loss from baseline (p < 0.0001). Bone mineral density was comparable between the relugolix combination therapy and placebo groups in LIBERTY 1 and 2. The distribution of the change in bone mineral density, including outliers, was similar for the relugolix combination therapy and placebo groups at 24 weeks, as assessed by dual energy x-ray absorptiometry (DXA). The overall incidence of adverse events in the relugolix combination and placebo groups was comparable in both studies.

The open-label extension study also met the primary endpoint with relugolix combination therapy demonstrating an 87.7% response rate at one year, showing the durability of the response observed in LIBERTY 1 and 2. In addition, women experienced, on average, an 89.9% reduction in menstrual blood loss from baseline. Changes in bone mineral density through one year, as assessed by DXA every three months, were consistent with LIBERTY 1 and 2. The overall incidence of adverse events in the relugolix combination and placebo groups was comparable in both studies.

Endometriosis

Our Phase 3 clinical program for endometriosis consisted of two multinational, replicate pivotal clinical studies (SPIRIT 1 and SPIRIT 2) of relugolix combination therapy (relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg) in women with pain associated with endometriosis. Eligible women who completed the SPIRIT 1 or SPIRIT 2 studies were offered the opportunity to enroll in an active treatment extension study in which all women receive relugolix combination therapy for an additional 80-week period, resulting in a total treatment period of up to 104 weeks, designed to evaluate the safety and sustained efficacy of longer-term treatment.

SPIRIT 1 and 2 met their co-primary endpoints (p < 0.0001) with 74.5% and 75.2% of women receiving relugolix combination therapy achieving clinically-meaningful reductions in dysmenorrhea (menstrual pain) compared with 26.9% and 30.4% of women receiving placebo at 24 weeks, respectively. 58.5% and 66.0% of women receiving relugolix combination therapy also achieved clinically-meaningful reductions in non-menstrual pelvic pain compared to 39.6% and 42.6% of women receiving placebo at 24 weeks, respectively. On average, women receiving relugolix combination therapy in SPIRIT 1 and 2 experienced a 73.3% and 75.1% reduction, respectively, on the Numerical Rating Scale from severe to mild pain. Relugolix combination therapy was generally well-tolerated with minimal bone mineral density loss over 24 weeks in SPIRIT 1 and 2. The overall incidence of adverse events in the relugolix combination and placebo groups was comparable in both studies.

Prostate cancer

Our Phase 3 clinical program for advanced prostate cancer consisted of a randomized, open-label, parallel-group, multinational clinical study (HERO) designed to evaluate the safety and efficacy of relugolix in men with androgen-sensitive advanced prostate cancer who required at least one year of continuous androgen deprivation therapy. Men were randomized 2:1 to receive a single loading dose of relugolix 360 mg followed by relugolix 120 mg once daily, or to treatment with leuprolide acetate 3-month depot injection, respectively.

Relugolix met the primary efficacy endpoint, with 96.7% of men treated with relugolix achieving sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks versus 88.8% of men treated with leuprolide acetate. Relugolix also met all six key secondary endpoints, demonstrating superiority to leuprolide acetate in rapid and profound suppression of testosterone and PSA response, in addition to improved testosterone recovery after discontinuation of treatment. Men in the relugolix group had a 54% lower risk of major adverse cardiovascular events (MACE) compared to men in the leuprolide acetate group (2.9% vs. 6.2%, respectively). In men with a reported history of MACE, the relugolix group had 80% fewer MACE events reported compared to the leuprolide acetate group (3.6% vs. 17.8%, respectively). The overall incidence of adverse events in the relugolix and leuprolide acetate groups was comparable.

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