Jazz Pharmaceuticals Presents Positive JZP-258 Phase 3 Study Data at World Sleep 2019
"We are pleased with the positive results from the Phase 3 study of JZP-258, which demonstrate the efficacy of JZP-258 for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy," said
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 and
The study design included an optimization and titration period of up to 12 weeks, a JZP-258 stable-dose period of two weeks, followed by 1:1 randomization to either JZP-258 or placebo for two 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).
During the double-blind withdrawal period, there was a significant increase in median weekly number of cataplexy attacks in participants randomized to placebo compared with participants randomized to JZP-258 (median [Q1, Q3]: 2.35 [0.00, 11.61] vs 0.00 [−0.49, 1.75], respectively; treatment difference, P<0.0001).
As expected, initial cataplexy rates differed based on prior therapy at study entry, with participants taking sodium oxybate only or sodium oxybate and an antidepressant/anticataplectic reporting the least cataplexy at study entry. In participants taking sodium oxybate only at study entry, cataplexy was stable with JZP-258 treatment across the open-label treatment titration and optimization period and the stable dose period (SDP). In those taking sodium oxybate and an antidepressant/anticataplectic at study entry, cataplexy was stable during initial titration of JZP-258, increased during taper and discontinuation of the other anticataplectic, and stabilized during SDP. In participants taking an anticataplectic other than sodium oxybate at study entry, cataplexy decreased during initial titration of JZP-258, increased during taper and discontinuation of the other anticataplectic and stabilized during SDP. In cataplexy treatment-naïve participants, cataplexy decreased consistently from week one of JZP- 258 titration through the end of SDP.
At the end of the double-blind withdrawal period, there was a significant increase in median ESS scores in participants randomized to placebo compared with participants randomized to JZP- 258 (median [Q1, Q3]: 2.0 [0.0, 5.0] vs 0.0 [−1.0, 1.0], respectively; treatment difference, P<0.0001). Additionally, both patient and clinician ratings of change in narcolepsy symptoms overall (PGIc and CGIc) indicated worsening in more participants randomized to placebo compared with participants randomized to JZP-258 ('Much Worse' or 'Very Much Worse' scores for placebo vs JZP-258: PGIc, 44.6% vs 4.3%; CGIc, 60.0% vs 5.9%; P<0.0001 [nominal]).
"It's encouraging to see these positive results from the Phase 3 study, as JZP-258 may represent an important and novel product candidate for people with narcolepsy with the benefit of a 92% reduction in sodium compared to sodium oxybate," said
The overall safety profile in the Phase 3 study of JZP-258 was consistent with that reported in clinical trials of sodium oxybate. The most common adverse events reported by ≥5% of participants while taking JZP-258 in the Phase 3 study were headache, nausea and dizziness. Two participants experienced serious adverse events that were considered by the investigator to be treatment-related (confusional state and visual hallucination after accidental JZP-258 overdose; muscle enzymes increased one day after the end of placebo treatment).
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
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.7,8,9 Although many emotions can potentially lead to cataplexy, those associated with mirth are usually the most potent.7 Cataplexy occurs in about 70% of people with narcolepsy.10 Presentation differs widely among people with narcolepsy, ranging from sporadic partial attacks triggered by laughter to frequent complete collapse brought about by a variety of emotions.6,7 Complete collapse is less common.8 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).7,8,9,10
JZP-258 is an investigational product being evaluated in adults 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). While the exact mechanism of action of JZP-258 is not fully understood, it is hypothesized that the therapeutic effects of JZP-258 on sleep/wake symptoms are mediated through modulation of GABAB during sleep.
About Jazz Pharmaceuticals plc
"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 belief that JZP-258, if approved, will provide a clinically meaningful benefit to patients prescribed oxybate and an important and novel product candidate for people with narcolepsy, and other statements that are not historical facts. These forward-looking statements are based on the company's current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the uncertain regulatory approval process, including the risk that the company's planned JZP-258 new drug application may not be submitted, accepted or approved by the
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- Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
- Overeem S, van Nues SJ, van der Zande WL, et al. The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. Sleep Med. 2011;12(1):12-18.
- Overeem S. The clinical features of cataplexy. In: Baumann CR, Bassetti CL, Scammell TE, eds. Narcolepsy: Pathophysiology, Diagnosis, and Treatment. New York, NY: Springer Science+Business Media; 2011:283-290.
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Jacqueline Kirby, Vice President, Corporate Affairs & Government Relations Ireland +353 1 697 2141, U.S. +1 215 867 4910; Investor Contact: Kathee Littrell, Vice President, Investor Relations Ireland +353 1 634 7887, U.S. +1 650 496 2717