0633 Efficacy and Safety of Low-Sodium Oxybate in Narcolepsy Patients With/Without Psychiatric/Neurologic Comorbidities

Abstract Introduction Prior studies report high incidences of psychiatric and/or neurologic comorbidities in patients with narcolepsy. Low-sodium oxybate (LXB; Xywav®) is an FDA-approved treatment for cataplexy or excessive daytime sleepiness in patients ≥7 years old with narcolepsy and for adults with idiopathic hypersomnia. This post hoc analysis of a phase 3 trial (NCT03030599) assessed LXB efficacy and safety in participants with narcolepsy with or without a medical history of psychiatric and/or neurologic comorbidities. Methods Participants were adults (18‒70 years) with narcolepsy with cataplexy. Participants optimized/titrated their LXB dose (up to 12 weeks) before a 2-week stable-dose period. During a 2-week double-blind randomized-withdrawal period, participants were either switched to placebo or continued LXB. Epworth Sleepiness Scale (ESS), average weekly number of cataplexy attacks, Patient Global Impression of Change (PGIc) scores, Patient Health Questionnaire-9 (PHQ-9) scores, and treatment-emergent adverse events (TEAEs) were evaluated in participants with and without psychiatric and/or neurologic comorbidities. Results Of 201 participants, 84 reported baseline comorbidities (most commonly depression, migraine headaches, anxiety, and headache non-migraine). Imbalances between subgroups were observed with regard to sex, race, ethnicity, and body mass index. Participants randomized to placebo in both subgroups showed worsening (increases) in ESS scores compared with participants who continued with LXB treatment (least squares mean differences, LXB vs placebo 95% CI, with comorbidities: −3.7 −5.6, −1.9, P=0.0001; without comorbidities: −2.0 −3.5, −0.6; P=0.0050). Participants randomized to placebo in both subgroups had increased weekly cataplexy attacks compared with those continuing LXB (location shift, LXB vs placebo 95% CI, with comorbidities: −4.0 −7.0, −1.1, P=0.0026; without comorbidities: −3.5 −9.1, −1.1, P 0.0001). Participants randomized to placebo in both subgroups showed worsening in PGIc scores compared with LXB (P 0.0001, for both). Symptoms of depression, as measured by PHQ-9 scores, remained stable in both subgroups. TEAEs and serious TEAEs occurred in 69 (82.1%) and 1 (1.2%) participants with comorbidities, and 84 (71.8%) and 3 (2.6%) without comorbidities, respectively. Conclusion In this post hoc analysis of a phase 3 trial in patients with narcolepsy, the efficacy and safety of LXB in participants with psychiatric and/or neurologic comorbidities were similar to those in participants without such comorbidities. Support (if any) Jazz Pharmaceuticals