Relugolix: Development Background and Mechanism of Action

Relugolix is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) drug used to treat prostate cancer in men and uterine fibroids in women. Its side effects include abnormal menstruation, hot flashes, sweating, headaches and decreased bone density. ‍It is a GnRH antagonist, that is, a gonadotropin-releasing hormone receptor antagonist.

Background

Uterine fibroids are one of the most common reproductive system tumors in women. Clinical data show that uterine fibroids are more common in women of childbearing age, more common in women aged 30 to 50, and the probability of women over 35 years old suffering from uterine fibroids is 30% to 40%. Uterine fibroids usually cause abnormal uterine bleeding, pelvic pain and pressure, urinary tract and intestinal symptoms, infertility and pregnancy complications.

Prostate cancer (PCa) is the second most common cancer in men worldwide, second only to lung cancer. According to statistics from the World Health Organization, there will be nearly 1.467 million new cases and 467,000 deaths worldwide in 2022. In my country, the incidence and mortality of PCa are showing a continuous growth trend, and PCa is gradually becoming an important disease affecting the health of middle-aged and elderly men in my country.

Relugolix Launch

On January 8, 2019, Relugolix developed by Takeda Pharmaceutical was approved for marketing in Japan by the Japan Pharmaceutical and Medical Devices Agency (PMDA). The trade name is Relumina (oral tablets, each tablet contains 40 mg of Relugolix), which is used to improve the following symptoms caused by uterine fibroids: menorrhagia, lower abdominal pain, back pain, anemia, and pain caused by endometriosis.

On December 18, 2020, the U.S. Food and Drug Administration (FDA) approved ORGOVYX Relugolix (oral tablets, each tablet contains 120 mg of Relugolix) developed by Myovant Sciences as the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist for the treatment of adult patients with advanced prostate cancer.

On May 26, 2021, the FDA approved the marketing of Myfembree, a Class 1 new drug jointly developed by Myovant Sciences and Pfizer (oral tablets, each tablet contains relugolix: estradiol: norethindrone acetate = 40mg: 1.0mg: 0.5mg), for the treatment of heavy bleeding related to uterine fibroids and pain caused by endometriosis.

According to statistics, the sales of relugolix and its compound preparations reached 1.465 billion yuan in 2022, and the market prospects are broad. The three specifications of the above-mentioned relugolix tablets were selected into the third batch of national encouraged generic drug catalogs on December 20, 2023.

Mechanism of action

Estrogen-dependent imbalance is the main cause of uterine fibroids and endometriosis in adolescent women, while androgen metabolism imbalance has a direct impact on the incidence of prostate cancer.

Endocrine therapy is an important treatment for the above tumors. Relugoli is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist that can block the binding of endogenous GnRH to its receptor, reduce the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and inhibit the secretion of sex hormones such as ovarian estradiol and progesterone, thereby improving various symptoms caused by uterine fibroids.

At the same time, the reduction in the release of LH and FSH can reduce the secretion of testosterone, thereby inhibiting the growth of prostate cancer cells.

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