FDA Okays First-in-Class Narcolepsy Drug Oveporexton

The US FDA has approved oveporexton (Orzeyful, Takeda), a first-in-class oral selective orexin receptor 2 agonist for the treatment of narcolepsy type 1 (NT1) in adults. NT1 is a rare, chronic disorder caused by loss of orexin neurons, which are involved in sleep regulation. Hallmarks of the disorder include excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, sleep paralysis, as well as cognitive difficulties. Current treatments primarily aim to improve wakefulness and control cataplexy but do not address the underlying pathophysiology. Oveporexton is the first drug to work by directly targeting the loss of orexin signaling that causes the disease. "For too long, people with narcolepsy type 1 have had to manage a complex, lifelong neuropsychiatric condition with treatments that only address pieces of it," Tiffany R. Farchione, MD, director of the Division of Psychiatry within the FDA's Center for Drug Evaluation and Research, said in a statement. "This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole," Farchione added. Multiple Symptom Improvement The safety and effectiveness of oveporexton were evaluated in two randomized, double-blind, placebo-controlled phase 3 trials involving 273 adults with NT1. Across both studies (FirstLight and RadiantLight), oveporexton led to statistically significant improvement across a broad range of NT1 symptoms compared to placebo at week 12. These included improvements in excessive daytime sleepiness, cataplexy, sleep paralysis, hallucinations, disrupted nighttime sleep and health-related quality of life, as previously reported by Medscape Medical News. Oveporexton has also been shown to improve cognition, including measures of attention, memory, and executive function. The drug was generally well-tolerated with a safety profile consistent across clinical studies. The most common side effects were insomnia, urinary urgency and frequency, and increased saliva production. It is taken orally twice daily and is contraindicated in patients taking strong CYP3A inhibitors. Its safety and effectiveness have not been established in patients younger than 18 years. Oveporexton previously received breakthrough therapy designation, and its application received priority review. Drug Enforcement Administration scheduling is underway and is expected to be completed within 90 days; the drug will become available after its controlled-substance classification is determined.