AbbVie reports success in Phase III trial (M12-665) of elagolix for Endometriosis

AbbVie in cooperation with Neurocrine Biosciences, Inc. announced positive top-line results from the first of two ongoing Phase III clinical trials, designed to evaluate the efficacy and safety of elagolix, a nonpeptide GnRH antagonist, in premenopausal women with Endometriosis.

Results from the trial show that after six months of treatment, both doses of elagolix (150 mg once daily and 200 mg twice daily) met the study's co-primary endpoints (p<0.001) of reducing scores of non-menstrual pelvic pain (nmpp) and menstrual pain (or dysmenorrhea), associated with endometriosis, at month three, as well as month six, as measured by the daily assessment of endometriosis pain scale. the observed safety profile of elagolix in this phase iii trial was consistent with observations from prior studies.>

The Phase III trial (M12-665) is a 24-week, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of elagolix in 872 women, age 18 to 49, with moderate-to-severe Endometriosis-associated pain. It is being conducted at approximately 160 sites in the United States, Puerto Rico and Canada.

A second Phase III, randomized, multinational, double-blind, placebo-controlled trial (M12-671) is evaluating elagolix in patients with moderate-to-severe endometriosis-related pain is ongoing and results are expected in late 2015.

Comment:Several companies have developed peptide GnRH agonists such as Lupron and Zoladex. However, since they are peptides, they must be injected via a depot formulation rather than the preferred oral route of administration. In addition, GnRH agonists can take up to several weeks to exert their desired effect once the initial stimulation has occurred, a factor not seen with the use of GnRH antagonists. Also GnRH agonists have shown a tendency to exacerbate the condition via hormonal flares and can be associated with hot flashes and the loss of bone mineral density. Orally active, nonpeptide GnRH antagonists potentially offer several advantages over injectable GnRH peptide drugs, including rapid onset of hormone suppression without a hormonal flare. Additionally, injection site reactions commonly observed in peptide depots are avoided and dosing can be rapidly discontinued if necessary � a clinical management option not available with long-acting depot injections. Importantly, by using GnRH antagonists, it may be possible to alter the level of pituitary GnRH suppression thereby titrating circulating estrogen levels. Using this approach, an oral GnRH antagonist may provide patients relief from the painful symptoms of Endometriosis while avoiding the need for the active management of bone loss.