Alkermes (ALKS) investor relations material

Study design and objectives

• Vibrance-2 was a randomized, double-blind, placebo-controlled phase 2 study evaluating alixorexton, an OX2R agonist, in adults with narcolepsy type 2 (NT2) and excessive daytime sleepiness (EDS).

• Participants were randomized to receive 10, 14, or 18 mg alixorexton or placebo once daily for 8 weeks, followed by an open-label extension (OLE) with flexible dosing.

• Dual primary endpoints were change in mean sleep latency (MWT) and Epworth Sleepiness Scale (ESS) from baseline to week 8.

• Exploratory endpoints included fatigue (PROMIS-Fatigue) and cognition (BC-CCI).

• Safety was assessed by monitoring adverse events, vital signs, labs, and ECGs.

Efficacy results

• Alixorexton significantly improved mean sleep latency on the MWT at week 8 versus placebo, with the 14 mg and 18 mg doses showing statistically significant differences.

• Clinically meaningful reductions in ESS scores were observed as early as week 2 and maintained through week 8, with the 18 mg dose reaching statistical significance versus placebo.

• Improvements in ESS continued during the OLE through week 13, with most participants reporting normal or mild EDS.

• Fatigue scores (PROMIS-Fatigue) improved as early as week 2 and continued through week 13, with significant differences for 14 mg and 18 mg doses at week 8.

• Cognitive impairment (BC-CCI) improved as early as week 2, with significant improvement for the 18 mg dose at week 8 and continued benefit through week 13.

Safety and tolerability

• Alixorexton was generally well tolerated, with most treatment-emergent adverse events (TEAEs) being mild to moderate in severity.

• No serious TEAEs or clinically meaningful changes in labs, vital signs, ECGs, or ophthalmic exams were observed.

• Most common TEAEs included pollakiuria, insomnia, micturition urgency, dizziness, and headache.

• TEAE rates were higher at higher doses but remained manageable, and no discontinuations due to TEAEs occurred.