3 global trials now testing alixorexton doses for 2 narcolepsy types

Alkermes has launched the Brilliance Studies, a Phase 3 clinical trial program that will evaluate the safety and effectiveness of alixorexton, its once-daily oral therapy candidate for people with narcolepsy types 1 and 2.

The new program builds on findings of Phase 2 trials showing that alixorexton could extend wakefulness and reduce excessive daytime sleepiness in both types of narcolepsy.

The new trials, spanning sites across North America, Europe, and the Asia Pacific region, will test different dosing schedules in both narcolepsy types, Alkermes stated in a company press release announcing the program.

“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,” said Craig Hopkinson, MD, chief medical officer and executive vice president of research & development at Alkermes.

Anyone interested can find more information on the program’s website.

Narcolepsy is a brain disorder that makes it hard to stay awake during the day. Type 1 (NT1) is caused by the loss of nerve cells that produce hypocretin, also called orexin, a signaling molecule that helps regulate sleep and wakefulness. When these cells are lost, sleep becomes dysregulated, and people often experience cataplexy, or sudden episodes in which muscle tone drops. In type 2 (NT2), hypocretin levels are normal, cataplexy doesn’t occur, and the cause is not fully understood.

Alixorexton aims to promote wakefulness in those with narcolepsy

Alixorexton works by activating the orexin 2 receptor, mimicking the effects of hypocretin. This is expected to promote wakefulness and reduce narcolepsy symptoms, regardless of whether deficient hypocretin signaling is the underlying cause of the disease. Alkermes is also developing the therapy for idiopathic hypersomnia, another sleep disorder.

Earlier this year, alixorexton received breakthrough therapy designation in the U.S. for NT1, a status that can help accelerate its development and approval. In a previous Phase 1b study, alixorexton safely promoted wakefulness in healthy volunteers and people with NT1.

After that, Alkermes began the Phase 2 Vibrance clinical trial program comprising two narcolepsy studies: Vibrance-1 (NCT06358950) and Vibrance-2 (NCT06555783), together involving nearly 200 patients.

According to top-line data from Vibrance-1, all alixorexton doses outperformed a placebo on both time spent awake and reductions in daytime sleepiness among 92 adults with NT1. Improvements appeared as early as week two. Treatment also reduced weekly cataplexy attack rates and improved patient-reported measures of disease severity, fatigue, and cognition.

In Vibrance-2, alixorexton led to meaningful improvements in time awake across all dose groups, with the higher doses reaching statistical significance compared with a placebo. Participants in the highest-dose group also showed a significant decrease in daytime sleepiness ratings.

Participants who completed the Vibrance trials could enroll in a long-term extension study (NCT06767683) to keep receiving alixorexton for as long as 100 weeks, or about two years. That study is ongoing.

Brilliance program testing oral therapy vs. a placebo

The Brilliance program comprises three studies. Two — Brilliance NT1, also called Study 302 (NCT07455383) and Study 304 — will focus on NT1, while the third, Brilliance NT2 (NCT07502443, or Study 303), will focus on NT2.

In all three trials, participants are assigned to receive alixorexton or a placebo daily for 12 weeks, or about three months. The NT1 studies will test two dosing regimens, while the NT2 study will test three.

The primary goal in all three studies is to assess whether alixorexton improves wakefulness compared with the placebo, using the maintenance of wakefulness test (MWT). Secondary endpoints include changes in Epworth Sleepiness Scale scores, patient-reported outcomes on fatigue, cognition, and disease severity, and safety. The NT1 studies also measure cataplexy rates.

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.

Each NT1 study aims to enroll approximately 150 participants, while the NT2 study targets an estimated 180. All three are recruiting across North America, the Asia Pacific region, and Europe, though specific site locations have not yet been released.

Participants who complete one of the Brilliance Studies can continue treatment with alixorexton in a long-term, safety study.

“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,” Hopkinson said.