Arena Pharmaceuticals, Inc. announced the initiation of patient screening in a phase 1 clinical trial of APD916, a novel oral drug candidate discovered by Arena that targets the histamine H3 receptor for the treatment of narcolepsy and cataplexy.

"There is a need for better tolerated, more effective therapies for narcolepsy, especially narcolepsy with cataplexy," said William R. Shanahan, M.D., Arena's vice president and chief medical officer. "Based upon preclinical data, we believe that APD916 may substantially improve the treatment of these potential orphan indications."

This randomized, double-blind and placebo-controlled Phase 1 trial is planned to enrol up to 72 healthy adult volunteers and will evaluate the safety, tolerability and pharmacokinetics of single-ascending doses of APD916.

APD916, a potent and selective inverse agonist of the histamine H3 receptor, is Arena's internally discovered drug candidate for the treatment of narcolepsy and cataplexy. The histamine H3 receptor is predominantly expressed in the brain, and inverse agonists of the H3 receptor increase the synthesis and release of histamine through inhibition of presynaptic autoreceptors. Enhanced histamine release plays an important role in arousal, and the histaminergic system is at least partly under the control of orexin/hypocretin neurons. Narcolepsy with and without cataplexy have been associated with orexin/hypocretin deficiency and low levels of histamine in cerebros fluid. Therefore, an H3 inverse agonist, by increasing central histamine activity, could be effective in the treatment of these conditions. APD916 was efficacious in multiple preclinical models, and the data suggest APD916 has potential utility in the treatment of narcolepsy with or without cataplexy.

Narcolepsy is a chronic neurological disorder caused by the brain's inability to regulate sleep-wake cycles normally. At various times throughout the day, people with narcolepsy experience irresistible bouts of sleep. If the urge becomes overwhelming, individuals will fall asleep for periods lasting from a few seconds to several minutes. Cataplexy, or the sudden loss of voluntary muscle tone triggered by emotional factors, is a symptom of narcolepsy and can cause a range of physical changes, from slurred speech to complete weakness of most muscles.

According to the National Institutes of Health, or NIH, narcolepsy is not rare, but it is an underrecognized and underdiagnosed condition. The NIH estimates that narcolepsy affects about one in every 2,000 Americans. Treatments are limited and consist of stimulant drugs to suppress daytime sleepiness and antidepressants for cataplexy. The only approved treatment for cataplexy in the United States is Xyrem (sodium oxybate), a DEA Schedule III drug.

Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs that target G protein-coupled receptors, an important class of validated drug targets, in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases.