Efficacy of Low-Sodium Oxybate in the Treatment of Idiopathic Hypersomnia: Evaluation of Treatment Response Based on the Epworth Sleepiness Scale and Idiopathic Hypersomnia Severity Scale Scores
Russell Rosenberg1, Abby Chen2, Teresa L. Steininger3, Wayne Macfadden4, Yves Dauvilliers5
1NeuroTrials Research, Inc., Atlanta, GA, USA, 2Jazz Pharmaceuticals, Palo Alto, CA, USA, 3Formerly Jazz Pharmaceuticals, Palo Alto, CA, USA, 4Jazz Pharmaceuticals, Philadelphia, PA, USA, 5Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital, Montpellier, France; University of Montpellier, INSERM Institute Neuroscience Montpellier (INM), Montpellier, France
Objective:
This post hoc analysis evaluated treatment response to lower-sodium oxybate (LXB; Xywav®) on Epworth Sleepiness Scale (ESS) and Idiopathic Hypersomnia Severity Scale (IHSS) scores in a phase 3 clinical trial (NCT03533114).
Background:
Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness, with sleep inertia and prolonged nighttime sleep as key symptoms in many patients.
Design/Methods:
Eligible participants with idiopathic hypersomnia began LXB treatment in an open-label titration and optimization period (OLT; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). The ESS and IHSS were completed at baseline, OLT week (W)1, W4, W8, end of OLT, and end of SDP, and response (ESS score ≤10 or decrease in ESS score of ≥4 points; IHSS score ≤22 or decrease in IHSS score of ≥4) was assessed.
Results:
Participants were treatment naive (n=47) or taking alerting agents at study entry (n=62). Among treatment-naive participants, the percentages achieving ESS score ≤10, ESS score decrease of ≥4 points, IHSS score ≤22, and IHSS score decrease of ≥4 points at W1 and end of SDP were, respectively, 13.0% and 87.2%, 26.1% and 87.2%, 26.1% and 80.9%, and 45.7% and 93.6%. Among participants taking alerting agents, the percentages achieving the same responses at W1 and end of SDP were, respectively, 21.0% and 83.9%, 33.9% and 95.2%, 24.2% and 82.3%, and 46.8% and 98.4%. Treatment-emergent adverse events (≥10%) included nausea, headache, dizziness, anxiety, and vomiting.
Conclusions:
Over 80% of participants achieved clinically meaningful responses on the ESS and IHSS; up to 95% (ESS) and 98% (IHSS) had score decreases ≥4 points at end of SDP. Response rate increased over the course of the study. The safety profile of LXB was consistent with that observed in narcolepsy.