Alkermes (ALKS) Study Update summary

Study overview and objectives

• Vibrance-2 was a randomized, double-blind, placebo-controlled phase II study evaluating once-daily alixorexton in 93 adults with narcolepsy type 2 (NT2) across 47 sites in the US, Europe, and Australia, with strong retention and most patients entering an open-label extension.

• Patients aged 18–70 with residual excessive daytime sleepiness and mean sleep latency ≤15 minutes were randomized to receive 10, 14, or 18 mg of alixorexton or placebo after a two-week washout.

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

• The study incorporated FDA feedback and excluded patients with significant comorbidities or other sleep disorders.

• Exploratory outcomes included patient-reported measures of cognition, fatigue, and disease severity, with an optional open-label extension and long-term safety study.

Efficacy results

• Statistically significant and clinically meaningful improvements in wakefulness (MWT) and excessive daytime sleepiness (ESS) were observed at 14 mg and 18 mg doses versus placebo.

• At week eight, ESS improved by -6.9 (14 mg) and -7.2 (18 mg) from baseline, with about 70% of subjects on 18 mg reaching normalization.

• Mean sleep latency increased by 8.3 (14 mg) and 8.2 (18 mg) minutes, with mean latency rising to 14–16 minutes from a baseline of about six minutes.

• Improvements in ESS were seen as early as week two and sustained through week eight; MWT improvements were consistent at early time points post-dose but more variable later in the day.

• Efficacy was robust despite high variability in the NT2 population, supporting advancement to phase III.

Safety and tolerability

• Alixorexton was generally well tolerated at all doses, with no treatment-emergent serious adverse events reported and most adverse events mild to moderate.

• Most common adverse events included polyuria/pollakiuria, insomnia, micturition urgency, dizziness, and headache.

• No dose response was observed in the frequency or severity of adverse events, and no dose-limiting toxicities were encountered.

• No safety signals were observed in hepatic, renal, vital signs, ECGs, or ophthalmic/visual exams.

• The safety profile allows for flexibility in dosing and supports potential for higher doses in future studies.