By Deborah Brauser
ATLANTA -- October 22, 2009 -- Elagolix, an oral nonpeptide gonadotropin-releasing hormone (GnRH) antagonist, can maintain oestradiol at low physiological concentrations for 6 months, at rates comparable to medroxyprogesterone acetate, without causing significant bone loss in patients with endometriosis.
The results from the Painful Endometriosis Trial (PETAL) study were reported here October 21 at the 65th Annual Meeting of the American Society for Reproductive Medicine (ASRM).
For the study, Dao Thai-Cuarto, PharmD, Department of Clinical Drug Safety, Neurocrine Biosciences, San Diego, California, and colleagues randomised 252 patients (mean age, 31.4 years) to receive elagolix 150 mg once daily (n = 84), elagolix 75 mg twice daily (n = 84), or subcutaneous medroxyprogesterone acetate 104 mg (n = 84) every 3 months.
All of the patients received treatment for 6 months and were followed for an additional 6 months. The Composite Pelvic Signs and Symptoms Scale (CPSSS) and Endometriosis Health Profile were administered monthly, and a visual analogue scale (VAS) was used to assess pain daily.
Results showed that peak and mean VAS scores, total CPSSS scores, and the health profile pain dimension were all improved by the first visit. These measures were also improved at week 24 for all groups compared with baseline (P < .0001), and the symptoms remained improved 6 months after the last dose was taken.
"Rapid and sustained improvement of endometriosis signs and symptoms occurred with elagolix, and the mean scores did not return to baseline severity after discontinuation of the study drug," explained Dr. Thai-Cuarto.
In addition, significant bone loss was not induced for the elagolix groups over the 6 months of treatment; the mean bone mineral density (BMD) change from baseline was -0.12% and did not exceed the -2.2% threshold. At week 24, the median oestradiol concentration was 45 pg/mL for the group receiving elagolix 150 mg and 29 pg/mL for the 75-mg group.
Elagolix was generally well tolerated, with headache and nausea the most common adverse events reported.
"One of the primary safety concerns with any drug that reduces oestradiol to a level that would be associated with relief of endometriosis pain is the risk that oversuppression would result in a reduction in BMD," said Dr. Thai-Cuarto. "That was not the case in the PETAL study."
"It also provided a clinically meaningful and statistically significant reduction in endometriosis pain from baseline, and the magnitude of improvement in endometriosis pain was robust and comparable to [medroxyprogesterone acetate]," she said.
The study was supported by Neurocrine Biosciences, Inc.
[Presentation title: PETAL Study: Safety, Tolerability, and Effectiveness of Elagolix, an Oral GnRH Antagonist for Endometriosis. Abstract P-81]
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