Phase 3 Brilliance Studies Initiated on Alixorexton for the Treatment of Narcolepsy Type 1 and Type 2

Alkermes today announced the initiation of the Brilliance Studies, a phase 3 program evaluating the safety and efficacy of alixorexton compared with placebo in adults with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2).¹ Alixorexton is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of NT1, NT2, and idiopathic hypersomnia (IH).

The Brilliance Studies program will consists of 3 randomized, double-blind, placebo-controlled, 12-week phase 3 studies evaluating once-daily and split-dose regimens of alixorexton: Brilliance NT1 (Study 302 and Study 304) and Brilliance NT2 (Study 303). Participants who complete 1 of the Brilliance Studies will be eligible to continue in a long-term, open-label, safety study.

"The initiation of the phase 3 Brilliance Studies program marks an exciting and important milestone for alixorexton. Building on the positive findings observed in our large phase 2 program across both narcolepsy type 1 and type 2, we are entering this pivotal stage with confidence. We look forward to evaluating alixorexton in both once-daily and split-dose regimens as we seek to optimize efficacy, safety and dosing flexibility in the development of a potential new treatment option for patients and providers," said Craig Hopkinson, MD, MBChB, the chief medical officer and executive vice president of Research and Development at Alkermes.

NT1

Participants in the 2 Brilliance NT1 studies will be randomized to receive 1 of 2 dosing regimens of alixorexton or placebo to be taken daily for 12 weeks. The primary endpoint of each study will assess whether participants taking alixorexton experience an increase in wakefulness compared with participants taking placebo, as measured by the change in mean sleep latency on the maintenance of wakefulness test (MWT). Secondary endpoints include change in Epworth Sleepiness Scale (ESS) score, mean weekly cataplexy rate, patient-reported outcomes related to fatigue, cognition and disease severity, and incidence of adverse events. Each study is expected to enroll approximately 150 participants with NT1 across sites in North America, Asia Pacific, and Europe.

NT2

Participants in the Brilliance NT2 study, Study 303, will be randomized to receive 1 of 3 dosing regimens of alixorexton or placebo to be taken daily for 12 weeks. The primary endpoint will assess whether participants taking alixorexton experience an increase in wakefulness compared with participants taking placebo alone, as measured by the change in mean sleep latency on the MWT. Secondary endpoints include change in ESS score, patient-reported outcomes related to fatigue, cognition and disease severity, and incidence of adverse events. The Brilliance NT2 study is expected to enroll approximately 180 participants with NT2 across sites in North America, Asia Pacific, and Europe.

Breakthrough Therapy Designation

Alixorexton was granted Breakthrough Therapy designation by the US Food and Drug Administration for the treatment of NT1 back in January 2026.^2,3 This designation was based on phase 1 and phase 2 clinical data, including positive results from Vibrance-1, a large phase 2 study evaluating alixorexton in 92 participants with NT1.

In the Vibrance-1 phase 2 study, alixorexton met the primary endpoint across all doses tested, demonstrating statistically significant, clinically meaningful and dose-dependent improvements from baseline compared to placebo in wakefulness on the MWT in patients with NT1. Alixorexton was generally well tolerated at all doses tested.

In Vibrance-2, 93 participants with NT2 were randomly assigned (1:1:1:1) to receive a once-daily dose of alixorexton (10 mg, 14 mg, or 18 mg) or placebo for 8 weeks. Once-daily alixorexton met the dual primary endpoints, demonstrating statistically significant and clinically meaningful improvements from baseline compared with placebo on the MWT and ESS at week 8.^4,5

References

1. Alkermes announces initiation of phase 3 Brilliance studies evaluating alixorexton for the treatment of narcolepsy type 1 and type 2. News release. April 1, 2026. Accessed April 1, 2026. https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-initiation-phase-3-brilliance-studies

2. Kuntz L. FDA grants breakthrough therapy designation to alixorexton for the treatment of narcolepsy type 1. Psychiatric Times. January 7, 2026. https://www.psychiatrictimes.com/view/fda-grants-breakthrough-therapy-designation-to-alixorexton-for-the-treatment-of-narcolepsy-type-1

3. Alixorexton granted breakthrough therapy designation by U.S. FDA for the treatment of narcolepsy type 1. News release. January 6, 2026. Accessed January 7, 2026. https://investor.alkermes.com/news-releases/news-release-details/alixorexton-granted-breakthrough-therapy-designation-us-fda

4. Alkermes announces positive topline results from Vibrance-2 phase 2 study of once-daily alixorexton in patients with narcolepsy type 2. News release. November 12, 2025. Accessed January 7, 2026. https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-positive-topline-results-vibrance-2-phase-2

5. Kuntz L. Alixorexton for treatment of narcolepsy type 2: new positive phase 2 data. Psychiatric Times. November 13, 2025. https://www.psychiatrictimes.com/view/alixorexton-for-treatment-of-narcolepsy-type-2-new-positive-phase-2-data