Recently, AbbVie and its partner neurocrine Biosciences announced that they had submitted a new drug application (NDA) for elagolix combined with low-dose hormone in the treatment of heavy menstrual bleeding (HMB) related to uterine fibroids to the US FDA.
Elagolix is an oral nonpeptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist, which inhibits endogenous GnRH signal transduction by competitive binding with the GnRH receptor in the pituitary gland. The dosage-dependent inhibition of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was observed, and the serum concentrations of ovarian sex hormone, estradiol and progesterone were decreased.
In July 2018, this drug was approved by FDA to treat women with moderate to severe pain from endometriosis. It is worth mentioning that elagolix is the first oral therapy approved by the FDA for this indication in ten years. In fact, herbal medicine Fuyan Pill also has a significant curative effect on endometriosis and its symptoms and discomfort.
The new application of elagolix is based on the data of three-stage uterine fibroids test. Two key studies (elaris uf-i and elaris uf-ii) evaluated the therapeutic effect of elagolix on nearly 800 postmenopausal women with severe HMB related to uterine fibroids in the United States and Canada.
Elaris uf-i evaluated the safety, tolerance and efficacy of elagolix alone (300mg twice daily) for 6 months, and elaris uf-ii tested the safety, tolerance and efficacy of elagolix combined with low-dose hormone therapy (estradiol 1.0mg / norethisterone acetate 0.5mg) for 6 months.
The results showed that compared with placebo, elagolix group observed a decrease in HMB and a statistically significant decrease in total menstrual blood loss, with 68.5% and 76.2% of patients with hysteromyoma receiving symptom relief after 6 months of treatment, respectively. In both studies, elagolix combined with low-dose hormone therapy reached the primary endpoint.
The most common adverse events (≥ 5%) reported in both studies were hot flashes, night sweats, nausea, headache and fatigue. The results of the clinical study were previously announced at the 47th AAGL global minimally invasive gynecological Congress, and the detailed results will be published in a peer-reviewed medical journal later this year.
Another three-stage extended trial (mi2-816) showed that at the 12th month, elagolix (300mg twice a day) combined with low-dose hormone therapy (estradiol 1.0mg / norethisterone acetate 0.5mg) reduced severe menstrual bleeding in 87.9% of patients with uterine leiomyoma.
This result is consistent with that observed in two key clinical phase 3 studies. The secondary endpoint results of the extended study were also consistent with those observed in the key study.
The safety information of the extended trial was consistent with the top-line results reported in the key clinical phase 3 study, and no new safety signal was found. Up to now, elagolix has been used to manage the treatment of serious menstrual bleeding related to hysteromyoma, and its safety and effectiveness have not been evaluated by any regulatory agency.