Corticotropin-Releasing Factor (CRF) Antagonist

Market Background

Not only is stress mentally and emotionally draining, it can take a physical toll on your body.  The key chemical in the regulation of the stress hormone cortisol is a brain hormone called corticotropin-releasing factor (CRF). This hormone is overproduced in patients with major depression and is thought to underlie the manifestation of many anxiety-related disorders, including social anxiety and irritable bowel syndrome (IBS). These two indications impact millions of people worldwide. In 2006, over 19 million Americans suffered from a debilitating anxiety disorder, representing $4.5 billion in prescription drug sales. Major Depressive Disorders account for $9 billion in prescription drug sales each year. For its part IBS affects approximately 30 million people in the United States, accounting for over $25 billion in direct and indirect costs each year.

Neurocrine's Approach

The receptors for CRF are found in specific brain regions that are responsible for the regulation of mood. CRF receptor antagonists offer a novel mechanism of action with the potential advantage of being more selective, potentially increasing efficacy and having a more rapid onset of action than current therapies while potentially reducing the number of side effects.  Neurocrine has characterized the CRF receptor system, identified additional members of this receptor family and holds a unique strategic position in the CRF field through a robust intellectual property portfolio and close relationships with leading experts in the neuropsychiatric field.

GlaxoSmithKline (GSK) Clinical Development Program

The CRF collaboration between Neurocrine and GSK has identified multiple unique high affinity and selective antagonists for the CRF1 receptor that are currently in clinical development for mood disorders and irritable bowel syndrome (IBS).

GSK advanced one of the lead CRF1 receptor antagonist compounds, 561679, into a Phase II depression study during 2008. This multicenter randomized, double-blind, placebo-controlled trial is designed to assess the safety and efficacy of 561679 in approximately 150 women with Major Depressive Disorder over six weeks of treatment. This study is scheduled to complete the treatment phase in mid-2010, with top-line results available thereafter.

Emory University of Atlanta and Mt. Sinai Medical Center in New York, in conjunction with GSK, through a grant from the National Institute of Mental Health, have recently initiated a second Phase II clinical trial evaluating 561679 in women with post-traumatic stress disorder. This study is randomized, double-blind, placebo-controlled trial which is expected to enroll approximately 150 patients for a six-week treatment period. This study is expected to take several years to complete.

Additionally, the National Institute on Alcohol Abuse and Alcoholism, in conjunction with GSK, is planning to initiate a Phase II clinical trial evaluating 561679 in stress-induced craving in alcoholic women with high anxiety. This study is a randomized, double-blind, placebo-controlled trial, expected to enroll 50 patients for a four week treatment period. This study is expected to take two years to complete.

GSK has also successfully completed a Phase I single dose escalating clinical trial with 586529, an additional CRF1 receptor antagonist compound..