Efficacy of Lower-Sodium Oxybate in the Treatment of Idiopathic Hypersomnia: Evaluation of Response Based on the Epworth Sleepiness Scale Score

Abstract: Introduction: This post hoc analysis evaluated response to open-label lower-sodium oxybate (LXB; Xywav®) treatment on Epworth Sleepiness Scale (ESS) scores in a phase 3 clinical trial (NCT03533114). Methods: Eligible participants with idiopathic hypersomnia began LXB treatment with an open-label titration and optimization period (OLT; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). The ESS was 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) was assessed. Results: Participants were treatment naive (n=47) or taking alerting agents at study entry (n=62). At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of ESS score ≤10 was 13.0%, 55.3%, 70.2%, 85.1%, and 87.2% (treatment-naive participants), respectively, and 21.0%, 56.5%, 65.6%, 74.2%, and 83.9% (participants taking alerting agents), respectively. At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of ESS score decrease of ≥4 points was 26.1%, 68.1%, 76.6%, 87.2%, and 87.2% (treatment-naive participants), respectively, and 33.9%, 64.5%, 78.7%, 88.7%, and 95.2% (participants taking alerting agents), respectively. Treatment-emergent adverse events (≥10%) included nausea, headache, dizziness, anxiety, and vomiting. Conclusions: Over 80% of participants achieved clinically meaningful responses (ESS score ≤10); up to 95% had ESS 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.Short Description: This analysis evaluated the response to open-label lower-sodium oxybate (LXB) treatment based on Epworth Sleepiness Scale (ESS) scores during titration and stable dosing in a phase 3 clinical trial in participants with idiopathic hypersomnia. The percentage of responders increased during open-label titration and optimization of LXB, and most participants achieved remission (ESS score of ≤10) and demonstrated a decrease in ESS score of ≥4 points at the end of the stable-dose period.Name of Sponsoring Organization(s): Jazz Pharmaceuticals