Jazz Pharmaceuticals Submits NDA for Therapy to Treat Excessive Daytime Sleepiness

Jazz Pharmaceuticals announced today it had redeemed its priority review voucher to submit a New Drug Application to the FDA on January 21, 2020; the company seeks approval for JZP-258, an investigational medication to treat cataplexy and excessive daytime sleepiness (EDS) in patients 7 years and older with narcolepsy.

The submission comes after the results found in the phase 3 global, double-blind, placebo-controlled, randomized-withdrawal, multicenter study on JZP-258, which demonstrated highly statistically significant differences in the weekly number of cataplexy attacks and Epworth Sleepiness Scale scores compared with placebo. Cataplexy is the most specific symptom of narcolepsy, which causes a sudden, generally brief loss of muscle tone with retained consciousness that is initiated by strong emotions such as laughter, surprise, and anger.

While the exact mechanism of action of JZP-258 is not fully understood, it is hypothesized that the medication’s therapeutic effects are caused through modulation of GABA_B during sleep. JZP-258 is a novel oxybate product candidate composed of the same oxybate concentration as sodium oxybate, sold as Xyrem^®, and contains other cations, including calcium, magnesium, and potassium.

Robert Iannone, MD, MSCE, executive vice president of research and development at Jazz Pharmaceuticals, highlighted that narcolepsy is a chronic disorder that may require lifelong therapy. The condition’s association with an increased risk of comorbid conditions, such as hypertension and cardiovascular disease, indicates the vital necessity of controlling sodium intake.

JZP-258 addresses this issue through its composition, which results in 92% (1000 to 1500 mg) less sodium than sodium oxybate. In fact, the substantial reduction could allow patients to achieve a daily sodium intake target of 2300 mg, and ideally 1500 mg, which is set by the American Heart Association.

"Jazz is committed to addressing unmet needs in sleep medicine, which includes working for nearly a decade to develop a novel oxybate formulation with a significant reduction in sodium," said Iannone.