Successful Phase III study of JZP 258, for the treatment of cataplexy and excessive daytime sleepiness.- Jazz Pharma

Jazz Pharmaceuticals plc announced that positive data from the Phase III study of its investigational medicine, JZP 258, for the treatment of cataplexy and excessive daytime sleepiness (EDS) in adults with narcolepsy were presented at World Sleep 2019 in Vancouver, Canada. Data from the study were presented in an oral presentation and in a poster presentation on September 24.

The Phase III 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 EDS in adults 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 Epworth Sleepiness Scale (ESS) score with JZP 258 compared to placebo. The study enrolled 201 participants and randomized 134 participants, comprising a heterogeneous population, which included those previously treated with sodium oxybate and na�ve to sodium oxybate, with or without other anticataplectic treatments. A randomized-withdrawal study design aims to measure efficacy � specifically, maintenance of effect � for participants who continue on active treatment � and worsening for participants randomized to placebo.

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-nave 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.>

The overall safety profile in the Phase III study of JZP 258 was consistent with that reported in clinical trials of sodium oxybate. The most common adverse events reported by greater than 5% of participants while taking JZP 258 in the Phase III 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).

Comment:Jazz is expected to file JZP 258 for FDA approval before the end of 2019 and to launch the drug in the second half of 2020 if Jazz uses a priority review voucher to speed the process. If it does not, the new drug is expected to launch in early 2021. Xyrem faces generic competition in 2023.