The U.S. Food and Drug Administration (FDA) has approved ORZEYFUL™ (oveporexton) for the treatment of narcolepsy type 1 (NT1), also known as narcolepsy with cataplexy, in adults.

The approval represents an important milestone for the narcolepsy community. ORZEYFUL is the first approved treatment designed to address the underlying orexin deficiency associated with NT1, rather than treating individual symptoms separately.

Understanding the Role of Orexin

Narcolepsy type 1 is a rare, chronic neurological condition caused by the loss of neurons that produce orexin, a chemical messenger that helps regulate wakefulness, sleep and muscle tone.

Because orexin plays an important role throughout the sleep-wake cycle, NT1 is a 24-hour condition. People may experience excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, sleep paralysis, hallucinations and cognitive challenges that can affect work, education, relationships and other aspects of daily life.

ORZEYFUL is an oral orexin receptor 2 agonist. It works by activating the receptor that orexin would normally stimulate, helping to restore orexin signaling in the brain.

Results From Clinical Trials

The FDA’s approval was supported by two Phase 3 clinical trials, FirstLight and RadiantLight, involving adults with NT1.

Compared with participants who received a placebo, those taking ORZEYFUL experienced statistically significant improvements across a range of NT1 symptoms. These included:

• Improved ability to remain awake during the day

• Reduced excessive daytime sleepiness

• Fewer cataplexy episodes

• Improvements in nighttime symptoms and overall narcolepsy severity

• Improved health-related quality of life

The most commonly reported side effects included insomnia, increased urinary frequency, urinary urgency and increased saliva production. ORZEYFUL should not be taken with strong CYP3A inhibitors. Individuals should speak with their healthcare provider about the treatment’s potential benefits, risks and possible medication interactions.

When Will ORZEYFUL Be Available?

Although ORZEYFUL has received FDA approval, it is not yet available to patients. Its controlled substance classification is currently under review by the Drug Enforcement Administration (DEA), a process expected to be completed within 90 days.

Takeda is preparing for the U.S. launch and expects ORZEYFUL to become available through a specialty pharmacy following completion of the DEA scheduling process, potentially by November 2026.

People interested in learning more or receiving availability updates can visit ORZEYFUL.com.

The approval of the first orexin-targeting treatment is a significant development for adults living with NT1 and for the broader narcolepsy community. As with every treatment decision, individuals are encouraged to speak with a qualified healthcare provider to determine whether ORZEYFUL may be appropriate for them.

Learn more through the FDA’s official announcement and Takeda’s approval announcement.