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

Abstract: Introduction: This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) treatment on Idiopathic Hypersomnia Severity Scale scores in a phase 3 clinical trial (NCT03533114). Methods: Eligible participants with idiopathic hypersomnia began LXB treatment with an open-label treatment titration and optimization period (OLT; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). The IHSS was completed at baseline, OLT week (W)1, W4, W8, end of OLT, and end of SDP, and response (IHSS score ≤22 or decrease in IHSS total 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 IHSS score ≤22 was 26.1%, 55.3%, 68.1%, 76.6%, and 80.9% (treatment-naive participants), respectively, and 24.2%, 53.2%, 60.7%, 71.0%, and 82.3% (participants taking alerting agents), respectively. At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of IHSS score decrease of ≥4 points was 45.7%, 80.9%, 83.0%, 97.9%, and 93.6% (treatment-naive participants), respectively, and 46.8%, 79.0%, 83.6%, 90.3%, and 98.4% (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 (IHSS score ≤22); up to 98% had IHSS 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 Idiopathic Hypersomnia Severity Scale (IHSS) scores during titration and stable dosing in a phase 3 clinical trial in participants with idiopathic hypersomnia. The IHSS assesses key idiopathic hypersomnia symptoms. The percentage of responders increased during open-label treatment, and most participants achieved remission (IHSS score ≤22) and demonstrated IHSS decreases of ≥4 points at end of the study period.Name of Sponsoring Organization(s): Jazz Pharmaceuticals