Oveporexton Boosts Wakefulness and Cuts Cataplexy in Narcolepsy Type 1, Phase 2 Trial Finds

"Oveporexton led to notable improvements in wakefulness, reduced daytime sleepiness, and lowered cataplexy episodes in individuals with narcolepsy type 1 over an eight-week treatment period," Yves Dauvilliers, University of Montpellier, INSERM Institute for Neurosciences Montpellier, Montpellier, France, and colleagues wrote.

Narcolepsy type 1 results from the degeneration of orexin-producing neurons in the brain, leading to insufficient orexin levels. Orexin is a neuropeptide critical for maintaining wakefulness and regulating REM sleep. Addressing this deficiency has been a key target in developing novel therapies.

The study, conducted as a randomized, placebo-controlled phase 2 trial, evaluated the efficacy and safety of various dosing regimens of oveporexton in adults diagnosed with narcolepsy type 1. 112 participants were enrolled, with 90 receiving one of four oveporexton doses and 22 receiving a placebo.

The primary outcome was the change in mean sleep latency, measured by the Maintenance of Wakefulness Test (MWT), from baseline to week 8. This test assesses the ability to stay awake during the day, with higher scores indicating better wakefulness.

The key findings of the study were as follows:

• Patients receiving oveporexton showed significant improvements in sleep latency, with increases ranging from 12.5 to 25.4 minutes, while the placebo group saw a decrease of 1.2 minutes.
• All dosing groups of oveporexton demonstrated statistically significant benefits in sleep latency compared to placebo.
• The Epworth Sleepiness Scale scores improved by 8.9 to 13.8 points across oveporexton groups, whereas the placebo group showed a 2.5-point reduction.
• Participants on 2 mg twice daily or 2 mg escalating to 5 mg daily regimens reported significantly fewer cataplexy episodes than those on placebo.
• Oveporexton was generally well tolerated among participants.
• Common adverse effects included insomnia (48%), urinary urgency (33%), and urinary frequency (32%).
• Most insomnia cases were resolved within one week.
• No hepatotoxic effects were observed during the trial.

"These findings emphasize the potential of oveporexton as a targeted therapy for narcolepsy type 1 by directly addressing orexin deficiency. Over the eight-week trial period, the drug improved wakefulness, reduced sleepiness, and lowered the frequency of cataplexy attacks," the researchers concluded. "Further studies are expected to evaluate long-term efficacy and safety."

Reference:

DOI: 10.1056/NEJMoa2405847