Alkermes (ALKS) investor relations material

Efficacy and clinical insights

• High probability of approval for Alixorexton in NT1 and likely label extension to NT2, with both showing statistically and clinically significant results.

• Vibrance-2 data revealed significant efficacy in NT2, with 70% of patients at 18mg achieving normal ESS scores, despite variability in MWT responses.

• Disease heterogeneity in NT2 is substantial, requiring flexible dosing strategies and larger doses for efficacy.

• Split dosing and dose flexibility are expected to be important in commercial use, with no dose-limiting toxicity observed at tested levels.

• Phase III studies will leverage learnings from Vibrance-2, with anchor QD dose and potential for split dosing to address patient variability.

Safety, tolerability, and dosing

• Safety profile confirmed in Vibrance-2, with mild to moderate side effects that attenuate over time.

• No dose-limiting toxicity encountered up to 25mg, providing flexibility for higher or split dosing.

• Tachyphylaxis appears to occur between day one and week four, with stable efficacy from week four to week eight.

• Dosing for phase III has been decided, with FDA recommending 40-50 patients per arm and likely three or four active dosing arms in NT2.

• Commercial strategy will include a range of doses for NT1 and NT2, offering more flexibility than competitors.

Competitive landscape and future directions

• Only two companies, including Takeda, have presented comparable data; both show strong efficacy and safety for orexin 2 receptor agonists.

• Differentiation expected through dosing flexibility and broader dose-response exploration.

• Phase III for IH (Vibrance-3) will use ESS as primary and IHSS as key secondary endpoints, with expectations of similar efficacy as in NT2.

• Oxybates will remain relevant for some patients, especially for nighttime consolidation, but orexins are expected to play a larger role in IH due to sleep inertia.

• Pharmacological advances may refine differential diagnosis and treatment personalization across NT1, NT2, and IH.