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*|
|*p<0.001 for Xyrem vs placebo.|
|Xyrem's most common side effects in adults|
|Rate with high-dose Xyrem (9mg)|
|Source: Xyrem label.|