New drug is the first to directly restore orexin signaling, targeting the underlying biological cause of narcolepsy type 1
The U.S. Food and Drug Administration today approved Orzeyful (oveporexton) tablets for the treatment of narcolepsy type 1 in adults. Orzeyful is the first medicine approved for narcolepsy type 1 as a complete disorder — addressing the full range of symptoms that define the condition — and the first 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,” said Tiffany R. Farchione, M.D., Director of the Division of Psychiatry within the FDA’s Center for Drug Evaluation and Research. “This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole.”
Narcolepsy type 1 is a rare, lifelong neuropsychiatric sleep disorder affecting an estimated 1 in 2,000 people in the United States. It is caused by the loss of brain cells that produce orexin, a chemical messenger that regulates wakefulness, sleep, and muscle tone. Without orexin, the brain struggles to maintain alertness or to control the boundary between sleep and waking. The result is a cluster of disabling symptoms, including excessive daytime sleepiness, cataplexy (sudden muscle weakness triggered by strong emotions such as laughter), sleep paralysis, hallucinations at the edge of sleep or waking, and disrupted nighttime sleep. Until today, no medicine had been approved for narcolepsy type 1 as a unified disorder, and none acted on the orexin system.
Rather than masking symptoms with stimulants or sedatives, Orzeyful directly activates the same brain receptor that the body’s own orexin would normally stimulate, restoring the missing signal. The medicine is taken as an oral tablet twice daily.
The effectiveness and safety of Orzeyful were evaluated in two randomized, double-blind, placebo-controlled 12-week studies enrolling 273 adults with narcolepsy type 1. Across both studies, patients taking Orzeyful 2 mg showed improvements in their ability to stay awake during the day compared with those receiving placebo. Patients also reported substantially less daytime sleepiness, a significant reduction in cataplexy episodes, and meaningful improvement across the full spectrum of narcolepsy symptoms, including sleep paralysis, hallucinations, and disrupted nighttime sleep.
The most common side effects were insomnia, increased urinary frequency, urgency to urinate, and increased saliva production. The rate of participants stopping treatment due to side effects was low. Patients should inform their healthcare professionals about all medicines they are currently taking, as Orzeyful should not be used at the same time as strong CYP3A inhibitors. The safety and effectiveness of Orzeyful have not been established in patients under 18 years of age. Orzeyful has been recommended for scheduling under the Controlled Substances Act and will be lawful to market following the scheduling decision issued by the Drug Enforcement Agency (DEA).
Orzeyful received Breakthrough Therapy Designation and Priority Review. Breakthrough Therapy Designation is granted to medicines that show early clinical evidence of substantial improvement over available therapies for serious conditions, allowing for more intensive FDA guidance and collaboration during development. Priority Review shortens the FDA’s target review time, and is reserved for medicines that, if approved, would offer significant improvements in the treatment of serious conditions.
The approval of Orzeyful for the treatment of narcolepsy type 1 was granted to Takeda Pharmaceuticals America, Inc.
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