Jazz Pharmaceuticals Announces Positive Top-line Results from Phase 3 Study of JZP-258 in Adult Narcolepsy Patients with Cataplexy and Excessive Daytime Sleepiness
The Phase 3 study demonstrated highly statistically significant differences in the primary endpoint that measured the change in the weekly number of cataplexy attacks and the key secondary endpoint of change in Epworth Sleepiness Scale (ESS) score with JZP-258 compared to placebo. In this study, patients were randomized to either continue JZP-258 or to receive placebo. Patients randomized to JZP-258 showed clinically meaningful maintenance of efficacy for both cataplexy and
The safety profile of JZP-258 is consistent with sodium oxybate. The most commonly reported treatment-emergent adverse events that occurred in ≥ 5% of patients who received JZP-258 were headache, nausea, dizziness, cataplexy, nasopharyngitis, decreased appetite, influenza, diarrhea and vomiting. Two patients experienced serious adverse events (SAEs) that were considered by the investigator to be treatment related.
Jazz will submit the Phase 3 study data for presentation at an upcoming medical meeting. Data from the completed Phase 3 study and interim data from the ongoing 24-week open-label, safety study will be included in the planned submission of a New Drug Application (NDA) to the
"Jazz is committed to developing new treatment options that serve unmet needs for patients living with sleep disorders, including JZP-258, a novel oxybate product candidate with 92% less sodium than sodium oxybate," said Jed Black, M.D., senior vice president, Sleep and CNS Medicine at Jazz Pharmaceuticals and adjunct professor, Stanford University Medical Center, Stanford Center for Sleep Sciences and Medicine. "We are deeply grateful to the patients and investigators who participated in this study, and we will meet with the
"Narcolepsy is a chronic, debilitating disease and is associated with an increased risk of comorbidities," said
About the Phase 3 Study
The Phase 3 study of JZP-258 was a global, double-blind, placebo-controlled, randomized-withdrawal, multicenter study evaluating the efficacy and safety of JZP-258 in the treatment of cataplexy in adult patients with narcolepsy. The primary endpoint was the change in the weekly number of cataplexy attacks and the key secondary endpoint was the change in the ESS score from JZP-258 and placebo over the randomized-withdrawal period. The study enrolled 201 patients and randomized 134 patients, comprising a heterogeneous patient population which included those previously treated with Xyrem, naïve to Xyrem, and with or without other anti-cataplectic treatments. A randomized-withdrawal study design aims to measure efficacy – specifically, maintenance of effect – for patients who remain on active treatment and worsening for patients who switch to placebo.
The study design included a titration period of up to 12 weeks, a JZP-258 stable-dose period of two weeks, followed by a 1:1 randomization to either JZP-258 or placebo for 2 weeks. After the completion of the double-blind, placebo-controlled treatment period, patients had the opportunity to receive JZP-258 in an optional 24 week open-label safety extension period. More information about the study design is available at www.clinicaltrials.gov (identifier: NCT03030599).
JZP-258 is an investigational product being evaluated in adult patients for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy, as well as for the treatment of idiopathic hypersomnia. JZP-258 is a novel oxybate product candidate with a unique composition of cations resulting in 92% less sodium than Xyrem® (sodium oxybate). The mechanism of action of JZP-258 is not fully understood, but it is hypothesized that the therapeutic effects of JZP-258 on sleep/wake symptoms are mediated through modulation of GABAB during sleep.
Narcolepsy is a chronic, debilitating neurological disorder characterized by excessive daytime sleepiness, and the inability to regulate sleep-wake cycles normally.1 It affects an estimated one in 2,000 people in the United States, with symptoms typically appearing in childhood. It is estimated that more than 50% of patients with narcolepsy have not been diagnosed.2 Studies have shown it may take 10 years or more for people with narcolepsy to receive a diagnosis.3 Excessive daytime sleepiness is the primary symptom of narcolepsy and is present in all people with the disorder.4 There are five primary symptoms of narcolepsy, including excessive daytime sleepiness, cataplexy, hallucinations, sleep paralysis and sleep disruption.5 While all patients with narcolepsy experience excessive daytime sleepiness, they may not experience all five symptoms.6,7 Excessive daytime sleepiness is characterized by the inability to stay awake and alert during the day resulting in unplanned lapses into sleep or drowsiness.2,4,8
Cataplexy, the most specific symptom of narcolepsy, is the sudden, generally brief (<2 minutes) loss of muscle tone with retained consciousness. It is usually triggered by strong emotions, such as laughter, surprise, or anger.6,7,9 Although many emotions can potentially lead to cataplexy, those associated with mirth are usually the most potent.6 Cataplexy occurs in about 70% of patients with narcolepsy.10 Presentation differs widely among patients, ranging from sporadic partial attacks triggered by laughter to frequent complete collapse brought about by a variety of emotions.6,7 Complete collapse is generally less common.7 More commonly, episodes of cataplexy involve only certain muscle groups, such as arms and legs (e.g., knees buckling), the head and neck (e.g., head dropping), or the face and jaw (e.g., sagging, slurred speech, eyelid drooping).6,7,9,10
"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995
This press release contains forward-looking statements, including, but not limited to, statements related to the company's planned submission of an NDA for JZP-258 with the
1. Thorpy M, Krieger A. Delayed diagnosis of narcolepsy: characterization and impact. Sleep Medicine. 2014;15(5):502–507.
2. Ahmed I, Thorpy, M. Clinical Features, Diagnosis and Treatment of Narcolepsy. Clin Chest Med. 2010;31(2):371-381.
3. Morrish E, King M, et al. Factors associated with a delay in the diagnosis of narcolepsy. Sleep Medicine. 2004;5(1):37-41.
5. Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ:
7. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
8. Ahmed I, Thorpy, M. Sleepiness: Causes, Consequences and Treatment, ed. Cambridge University Press. 2011:36-49.
9. Overeem S,
10. Overeem S. The clinical features of cataplexy. In: Baumann CR, Bassetti CL, Scammell TE, eds. Narcolepsy: Pathophysiology, Diagnosis, and Treatment. New
View original content to download multimedia:http://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-positive-top-line-results-from-phase-3-study-of-jzp-258-in-adult-narcolepsy-patients-with-cataplexy-and-excessive-daytime-sleepiness-300819008.html
Media, Jacqueline Kirby, Vice President, Corporate Affairs & Government Relations, Ireland +353 1 697 2141, U.S. +1 215 867 4910, or Investors, Kathee Littrell, Vice President, Investor Relations, Ireland +353 1 634 7887, U.S. +1 650 496 2717