Summary of Alkermes FY Conference Call (December 04, 2025) Company Overview - **Company**: Alkermes (NasdaqGS:ALKS) - **Focus**: Development of Elixirxton, an orexin 2 receptor agonist for the treatment of narcolepsy (NT1 and NT2) and idiopathic hypersomnia (IH) Key Points Industry Context - **Orexin Receptor Agonists**: Emerging therapeutic category for sleep disorders, particularly narcolepsy and hypersomnolence conditions [1][2][3] Clinical Trial Insights - **Vibrance-1 and Vibrance-2 Studies**: - Vibrance-1 data indicates a high probability of Elixirxton's approval for NT1 [4][5] - Vibrance-2 data shows statistically significant and clinically meaningful changes, supporting the drug's potential for NT2 [6][7] - 70% of patients at the 18-milligram dose achieved normalcy on the Epworth Sleepiness Scale (ESS) [30] Efficacy and Potency - **Efficacy Variability**: - NT2 patients exhibit a wide range of responses, complicating efficacy assessments [27][38] - The study revealed that while some patients did not respond on the Maintenance of Wakefulness Test (MWT), they showed improvement on the ESS [28][30] - **Disease Heterogeneity**: - NT2 is viewed as a distinct condition from NT1, necessitating different treatment approaches [33][38] Dosing Strategy - **Dosing Flexibility**: - Alkermes is considering a range of doses for both NT1 and NT2, with potential for split dosing to enhance patient control over wakefulness [49][60] - A once-daily (QD) dose is expected to be a strong anchor, but flexibility for top-up doses may be beneficial [50][54] - **Phase 3 Trials**: - Decisions on dosing for phase 3 trials have been made, with expectations of 40 to 50 patients per arm [170][166] Competitive Landscape - **Comparison with Competitors**: - Alkermes acknowledges the presence of other orexin receptor agonists, particularly from Takeda, and emphasizes the importance of safety and tolerability in their data [144][155] - Alkermes aims to differentiate through dosing flexibility and a broader range of dosing options [163] Safety and Tolerability - **Safety Profile**: - Vibrance-2 confirmed the safety hypothesis, with no dose-limiting toxicities observed at tested doses [132][60] - The drug is expected to be well-tolerated, with mild to moderate side effects that may attenuate over time [154][159] Future Directions - **IH Study Insights**: - Anticipation of similar efficacy in IH patients based on learnings from NT2 studies [178][182] - The study will focus on the signal of wakefulness using the IH Sleep Scale (IHSS) and ESS as primary endpoints [191][198] Role of Oxybates - **Oxybate Products**: - Alkermes sees a continued role for oxybates in the treatment landscape, particularly for patients who prefer nighttime consolidation of sleep [210][218] - The company acknowledges that not all IH patients will require oxybates, but some may benefit from their use [221] Additional Considerations - **Clinical Measurement Tools**: - The Epworth Sleepiness Scale is widely used but may be supplemented with more specific measures of cognition and fatigue in future studies [123][127] - **Market Potential**: - The overall market for orexin receptor agonists is expected to grow, accommodating multiple drugs and treatment options [144][145] This summary encapsulates the key insights from the Alkermes FY Conference Call, highlighting the company's strategic focus on Elixirxton and its implications for the treatment of narcolepsy and hypersomnolence disorders.