AT WCE 2017
VANCOUVER – An oral agent reduced dysmenorrhea and nonmenstrual pelvic pain in endometriosis patients, with more fine control over estrogen levels than historically seen with injectable gonadotropin-releasing hormone (GnRH) agonists, according to findings from two randomized controlled trials.
Elagolix is an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist being developed by Neurocrine Biosciences and AbbVie. Its dose can be adjusted in an attempt to achieve estrogen levels in the optimal “therapeutic window” that controls endometriosis pain while reducing menopausal symptoms, according to Hugh S. Taylor, MD , professor of obstetrics, gynecology and reproductive services at Yale University, New Haven, Conn., and chief of obstetrics and gynecology at Yale–New Haven Hospital, who presented the research at the World Congress on Endometriosis.
“One of the frustrations is there haven’t been enough treatment options available,” Dr. Taylor said.
Results from two phase III clinical trials, simultaneously published in the New England Journal of Medicine, show that two different doses of elagolix – 150 mg once daily or 200 mg twice daily – improved moderate or severe endometriosis-associated pain. However, patients taking the drug experienced heightened frequencies of hot flushes and increased serum lipid levels, and decreases from baseline in bone mineral density (N Engl J Med. 2017 May 19. doi: 10.1056/NEJMoa1700089 ).
Still, the two doses give physicians options in tailoring the drug for their patients, Dr. Taylor said. The key is to keep the levels within the therapeutic window. “That’s always been the goal, and now we have a drug that does that. You can customize it for your patient, using the stronger dose for those who need it,” he said.
He described the results from two parallel clinical trials, one conducted in the United States and Canada ( Elaris Endometriosis I , n = 872) and one conducted at 187 sites on five continents ( Elaris Endometriosis II , n = 817).
After a washout period of hormonal therapies, premenopausal women aged 18-49 years with surgically confirmed endometriosis and moderate or severe endometriosis-associated pain were randomized to receive 150 mg of elagolix once daily, 200 mg of elagolix twice daily, or placebo. In all, 653 (74.9%) completed treatment in Elaris EM-I and 632 (77.4%) completed treatment in Elaris EM-II.
Patients were allowed to use NSAIDs (500 mg of naproxen) or an opioid, or both, as needed. Dr. Taylor reported the results after 6 months of treatment.
Both doses of the drug outperformed placebo in reducing dysmenorrhea at 3 months. In Elaris EM-I, 75.8% in the high-dose group and 46.4% in the low-dose group had a clinically significant reduction in dysmenorrhea and decreased or stable use of analgesics at 3 months, compared with 19.6% in the placebo group. In Elaris EM-II, 72.4% in the high-dose group and 43.4% in the low-dose group achieved a clinically significant reduction, compared with 22.7% in the placebo group (P less than .001 for all comparisons).
For nonmenstrual pelvic pain, the two doses of elagolix again bested placebo. In Elaris EM-I, 54.5% in the high-dose group and 50.4% in the low-dose group achieved a clinically significant reduction and a decreased or stable use of analgesics, compared with 36.5% on placebo (P less than .001 for all). In Elaris EM-II, 57.8% in the high-dose group and 49.8% in the low-dose group achieved a clinically significant response, compared with 36.5% in the placebo group (P less than .001 and P = .003, respectively).
The responses were sustained at 6 months for both outcomes.
In Elaris EM-I, hot flushes were reported by 7.0% of the placebo group, 23.7% of the low-dose group, and 42.3% of the high-dose group (P less than .001). In Elaris EM-II, they were reported in 10.3% of the placebo group, 22.6% of the low-dose group, and 47.6% of the high-dose group (P less than .001).
Patients in the elagolix groups experienced increases in total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, though the researchers noted that less than 20% of participants in each group had LDL levels higher than 160 mg/dL or triglycerides levels higher than 200 mg/dL at any point during treatment.
There were also decreases in bone mineral density in the elagolix groups, but after 6 months of treatment, a z score of –1.5 or less at the lumbar spine occurred in fewer than 5% of women in the elagolix groups.
The drug should provide a more palatable option to GnRH agonists, according to Dr. Taylor. “This is a big step forward, very effective and much more tolerable. I think having an oral, rapidly acting, reversible drug, with a couple of doses available, will make this much more widely accepted and just as effective.”
The study was sponsored by AbbVie. Dr. Taylor and other researchers on the study reported financial ties to AbbVie and other pharmaceutical companies.
