0637 Composite Response with Once-Nightly Sodium Oxybate: Symptom Improvement in Participants with Narcolepsy Type 1

Abstract Introduction A novel once-nightly formulation of sodium oxybate (ON-SXB; LUMRYZ™) was investigated in patients with narcolepsy type 1 (NT1) and 2 (NT2) in the phase 3 REST-ON trial (NCT02720744). ON-SXB treatment resulted in statistically significant improvements vs placebo for the coprimary endpoints of change from baseline in mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and number of weekly cataplexy attacks, as well as the secondary endpoint of improved excessive daytime sleepiness (EDS) using the Epworth Sleepiness Scale (ESS; all P< 0.001 vs placebo). The objective of this post hoc analysis was to assess the proportion of participants with NT1 achieving clinically significant improvement on a composite of these endpoints. Methods Participants (aged ≥16 years with NT1 or NT2) who had continuing presence of EDS (sleep latency < 11 min on the MWT and ESS score >10) and continuing cataplexy (average of 8 episodes/week) were randomized 1:1 to ON-SXB or placebo. Doses were 4.5 g week 1; 6 g weeks 2−3; 7.5 g weeks 4−8; and 9 g weeks 9−13. Clinically significant improvement thresholds per the 2021 American Academy of Sleep Medicine Clinical Practice Guidelines for each endpoint were defined as follows: MWT (2-min improvement), CGI-I (1-point improvement), cataplexy (25% decrease), or ESS (2-point improvement) and examined for each dose. Results Mean age of participants with NT1 was 32.1 years, 72.8% were female, and 76.5% were white. The modified intent-to-treat population included 145 participants with NT1 (ON-SXB, n=73; placebo, n=72). At week 13 (9 g), more participants treated with ON-SXB vs placebo had clinical improvement in ≥2 endpoints (87.3% vs 62.9%; P< 0.01), ≥3 endpoints (76.4% vs 43.5%; P< 0.001), and in all 4 endpoints (47.3% vs 14.5%; P< 0.001). Similar results were observed at all doses. Conclusion These data support the robust clinical efficacy of ON-SXB, a once-at-bedtime oxybate for treatment of cataplexy or EDS in adults with narcolepsy, using multiple disease state metrics compared with placebo. Support (if any) Avadel Pharmaceuticals