AbbVie and Neurocrine Biosciences recently announced that the US FDA has approved Oriahnn (elagolix, estradiol, norethindrone acetate capsules; elagolix capsules) as the first non-surgical oral drug for the treatment of premenopausal women and uterine muscle A large number of menstrual bleeding related to the tumor, the duration of treatment can be up to 24 months.
Uterine fibroids, also known as leiomyomas or fibroids, are estrogen and progestin-dependent uterine non-cancerous tumors, which are non-cancerous hormone-responsive muscle tissue tumors. Fibroids are the most common type of abnormal growth in the female pelvis and the most common type of benign tumors in women of childbearing age. They can affect 70% of white women over the age of 50 and 80% of African-American women in the United States. The size, shape, number and location of fibroids can change during growth and can be asymptomatic, but in some women it can cause symptoms such as menstrual bleeding. Traditionally, uterine fibroids are mainly treated by surgery (hysterectomy, hysteromyomectomy), which is the main reason for hysterectomy in the United States. Other treatments include endometrial ablation, uterine artery embolization, magnetic resonance imaging-guided focused ultrasound, and drug treatments such as oral contraceptives, progestins, selective progesterone receptor modulators, and gonadotropin-releasing hormone (GnRH) agonists and antagonists.
The approval is based on the results of two randomized, double-blind, placebo-controlled phase 3 clinical trials of ELARIS UF-I and ELARIS UF-II for uterine fibroids. Two similar studies are designed to evaluate elagolix twice daily 300 mg combined with hormone "supplemental therapy" (estradiol 1 mg and norethindrone acetate 0.5 mg once daily; to replace endogenous hormones with reduced levels) in women with fibroids-related bleeding. The trial set up the elagolix alone group (300 mg twice daily) to evaluate the effect of combined hormone replacement therapy on the estrogen-lowering effect of elagolix. The two studies enrolled nearly 800 premenopausal women with severe menstrual bleeding (severe menstrual bleeding) associated with uterine fibroids at approximately 100 clinical sites in the United States and Canada. The primary end point was within the last month of treatment, measured by the basic heme method, elagolix monotherapy or elagolix combined with hormone therapy compared with placebo, the patient's menstrual blood loss was less than 80 ml, and from baseline to the last month Menstrual blood volume is reduced by at least 50%.
A total of 412 women in the UF-1 trial and 378 women in the UF-2 trial were randomized and received elagolix or placebo treatment. The results showed that in the two trials of elagolix combined with hormone replacement therapy, 68.5% of patients with UF-1 reached the primary end point and 76.5% of UF-2 reached the end point; in the group receiving only elagolix monotherapy, UF-1 The proportion of patients who met the endpoint criteria in UF-2 and 8UF was 84.1% and 77%, respectively, while the proportion of patients who met the endpoint criteria in the placebo group was 8.7% and 10%, respectively (P<0.001). Compared with placebo, elagolix combined with hormone therapy more frequently causes hot flashes (in UF-1 and UF-2) and uterine bleeding (in UF-1). But hormonal therapy weakens the low estrogen effect of elagolix, especially to reduce its density of bone minerals.
The researchers published data from two studies in the New England Journal of Medicine and stated that Oriahnn reached a clinically meaningful primary endpoint of reduction in bleeding. About 70% of women no longer experience severe menstrual bleeding, compared with only 10% in the placebo group (both trials P less than 0.001). Oriahnn also reduced heavy menstrual bleeding caused by uterine fibroids by 50% within the first month after use.
But Oriahnn also has certain side effects. The two companies indicated in the announcement that the drug may increase the risk of heart disease, stroke or blood clots in patients, especially those who are over 35 years old, smokers and have a history of hypertension. In addition, due to the risk of persistent and irreversible bone loss, the use of Oriahnn needs to be limited to 24 months.
Oriahnn is an oral drug composed of elagolix and E2/NETA (estradiol/norethindrone acetate), which helps patients balance the reduction of massive bleeding and the production of estrogen-related side effects. Among them, elagolix is an oral, small molecule GnRH receptor antagonist, by inhibiting the pituitary gonadotropin-releasing hormone receptor, and ultimately reducing the level of circulating gonadotropin.
Elagolix (trade name Orilissa) is also a drug jointly developed by AbbVie and Neurocrine Biosciences. It is used in female patients with menorrhagia associated with uterine fibroids and moderate to severe pain associated with endometriosis.