Devil will be in the detail with Jazz’s Xyrem follow-on

Jazz’s efforts to extend its Xyrem narcolepsy franchise have been boosted with the pivotal trial success of its low-sodium follow-on, JZP-258. However, Jazz did not disclose any data from the study, saying only that JZP-258 significantly reduced cataplexy attacks versus placebo. The newcomer will need to show better tolerability than Xyrem, and at least similar efficacy, if Jazz is to switch patients to JZP-258 before Xyrem comes off patent in 2023. JZP-258 is supposedly safer as it contains 92% less sodium than Xyrem, which can push patients over their recommended sodium intake; this is particularly problematic in a population already at risk of cardiovascular disease. On safety, Jazz would only say that JZP-258 had a similar profile to Xyrem; worryingly, two patients in the randomised withdrawal study had serious adverse events deemed to be treatment related. Xyrem itself has a black-box warning, and is also linked with side effects including depression and anxiety – despite this it brought it $1.4bn last year. The sellside does not seem convinced that JZP-258 can compete with generics, with EvaluatePharma consensus putting 2024 sales of the newcomer at just $297m. Jazz is also studying JZP-258 in idiopathic hypersomnia.

Setting the bar for JZP-258
Xyrem's efficacy in its randomised withdrawal trial
  Median cataplexy attacks over 2-week withdrawal period*
Placebo (n=29) 21
Xyrem (n=26) 0
*p<0.001 for Xyrem vs placebo.
   
Xyrem's most common side effects in adults
  Rate with high-dose Xyrem (9mg)
Nausea 20%
Dizziness 15%
Vomiting 11%
Somnolence 8%
Source: Xyrem label.

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