AbbVie initiates Phase III trial of Elagolix (a gonadotropin-releasing hormone (GnRH) receptor antagonist) to treat uterine fibroids.

AbbVie in cooperation with Neurocrine Biosciences, Inc. announced the initiation of the first of two planned Phase III clinical studies evaluating the safety and efficacy of Elagolix ( a gonadotropin-releasing hormone (GnRH) receptor antagonist) alone or in combination with add-back therapy compared to placebo. These studies are designed to assess the change in menstrual blood loss utilizing the alkaline hematin method, comparing baseline to month six of treatment. Additional secondary efficacy endpoints are being evaluated; including assessing changes in fibroid volume, monthly blood loss and hemoglobin levels. Bone mineral density will also be assessed.

The Elagolix Phase III uterine fibroid clinical development program is part of AbbVie's pipeline and includes two replicate, randomized, parallel, double-blind, placebo-controlled clinical trials. Each trial is expected to enroll approximately 400 subjects for an initial six-month placebo-controlled dosing period, after which, subjects who are eligible will have an option to continue for an additional six-month dosing period in a safety and efficacy extension study.

Comment: Gonadotropin-releasing hormone, or GnRH, is a peptide that stimulates the secretion of the pituitary hormones that are responsible for sex steroid production and normal reproductive function. Researchers have found that chronic administration of GnRH agonists, after initial stimulation, reversibly shuts down this transmitter pathway and is clinically useful in treating hormone-dependent diseases such as endometriosis and uterine fibroids. Several companies have developed peptide GnRH agonists on this principle, 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. More importantly, until the desired effects are maximal, GnRH agonists have shown a tendency to exacerbate the condition via a hormonal flare. The ultimate profound suppression effect observed with GnRH agonists is similar to that seen after menopause and can be associated with hot flashes and the loss of bone mineral density.