Higher-Dose Xywav Treatment for Narcolepsy Linked to Self-Reported Improvements in Cognition and Function

Higher doses of Xywav (low-sodium oxybate; Jazz Pharmaceuticals, Dublin, Ireland) above 9 g/night were associated with improvements in cognitive complaints, functional outcomes, and work productivity in individuals with narcolepsy. These findings from the prospective, open-label phase 3b/4 Jazz DUET study (NCT05875974) were presented at the 2026 American Academy of Neurology (AAN) Annual Meeting. Participants identified by investigators as candidates for dose escalation experienced reductions in disease severity and patient-reported symptom burden after titration to optimized doses up to 12 g/night.

In the study, participants with narcolepsy underwent an initial assessment period on Xywav 9 g/night, followed by a 2- to 8-week titration phase and a 2-week stable-dose period at individualized doses exceeding 9 g/night. Outcomes were evaluated using patient-reported measures, including the Patient Global Impression of Severity (PGI-S) and Change (PGI-C), the British Columbia Cognitive Complaints Inventory (BC-CCI), the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), and the Work Productivity and Activity Impairment questionnaire specific to narcolepsy (WPAI:SHP).

A total of 48 participants received Xywav doses greater than 9 g/night (mean dose, 11.1 g/night at stable dosing). At higher doses, fewer participants rated their disease as severe on the PGI-S compared with the 9 g/night assessment, and 92.3% reported overall improvement on PGI-C.

Key Findings

• Mean BC-CCI scores improved from 6.9 to 5.1 (least squares mean difference, −1.84; P=.0004), with fewer participants reporting moderate-to-severe cognitive complaints (34.1% to 18.2%).
• Functional outcomes improved, with FOSQ-10 scores increasing from 13.6 to 14.8 (LSM difference, 1.3; P=.0014).
• Work productivity improved, including reductions in presenteeism (−13.5%; P=.0058), overall work impairment (−12.5%; P=.0191), and activity impairment (−22.2%; P<.0001), while absenteeism was unchanged.
• The proportion of participants reporting severe disease decreased from 61.4% at 9 g/night to 29.5% at >9 g/night.
• Treatment-emergent adverse events were consistent with the known safety profile of Xywav.

Source

Schneider L, Ruoff C, Plante D, et al. Changes in self-reported cognitive complaints, functional impairments, work productivity, and symptom severity in participants with narcolepsy after treatment with greater than 9 gram dosages of low-sodium oxybate in the DUET study. Presented at: American Academy of Neurology Annual Meeting; April 18-22, 2026; Chicago, IL.