Efficacy and Safety of Lower-Sodium Oxybate in an Open-Label Titration Period of a Phase 3 Clinical Study in Adults with Idiopathic Hypersomnia.

To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18-75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10-14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). The safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1-4, n = 87 [56.5%]; weeks 13-16, n = 39 [31.7%]). During open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.

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© 2022 Thorpy et al.

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MJT has received research/grant support and consultancy fees from Jazz Pharmaceuticals, Harmony Biosciences, Balance Therapeutics, Axsome Therapeutics, NLS Pharmaceuticals, XW Pharma, Suven Life Sciences, Takeda Pharmaceutical, Idorsia Pharmaceuticals, Eisai Pharmaceuticals, and Flamel/Avadel Pharmaceuticals. IA has participated in an advisory board for Idorsia and received compensation for participating in a speaker bureau for UCB Pharma. N F-S has served on an advisory committee for Jazz Pharmaceuticals and participated in clinical trials supported by Jazz Pharmaceuticals, Suven, Harmony, and Takeda. AMM has received research funding from the National Institutes of Health, Geisinger Health Plan, and the Klarman foundation; has been a site PI for Avadel Pharmaceuticals and Jazz Pharmaceuticals; and has served on an advisory board/speakers bureau for Jazz Pharmaceuticals and advisory boards for Avadel Pharmaceuticals and Harmony Biosciences; he is also a medical advisor for Neura. KŠ has served on the speakers’ bureau for Sanofi, Angelini, and Stada and as a consultant for AOP Orphan, and participated in advisory boards for UCB and in clinical trials for Jazz Pharmaceuticals, Flamel-Avadel, and Luitpold Pharmaceuticals. PC, LH, AC, and AS are full-time employees of Jazz Pharmaceuticals who, in the course of this employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals, plc. JB is a part-time employee of Jazz Pharmaceuticals and shareholder of Jazz Pharmaceuticals plc. DC is a former full-time employee of Jazz Pharmaceuticals who, in the course of this employment, received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals, plc. RKB has served as a consultant for Jazz Pharmaceuticals, Harmony Biosciences, Balance Therapeutics, Avadel Pharmaceuticals, Takeda, and Oventus, and on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Eisai. He also reports grants for industry-funded research from Avadel, BresoTec, Idorsia, Suven, Jazz, Balance, Vanda, Merck, Eisai, Philips, Fresca, Takeda, Liva Nova, Roche, Sommetrics, NLS, Sanofi, and Apnimed. He is a shareholder of WaterMark Medical. YD is a consultant for and has participated in advisory boards for Jazz Pharmaceuticals, Orexia, UCB Pharma, Avadel, Idorsia, Takeda, Theranexus, and Bioprojet. The authors report no other conflicts of interest in this work.