Key takeaways:

• The FDA approved Orzeyful (oveporexton) for adults with narcolepsy type 1, making it the first drug to directly target the underlying loss of orexin signaling.
• In 12-week clinical trials, the twice-daily oral tablet improved wakefulness and reduced cataplexy, sleep paralysis, and hallucinations compared to placebo.
• The drug received Breakthrough Therapy Designation and Priority Review and awaits scheduling by the DEA before it can be marketed by Takeda Pharmaceuticals.

The US Food and Drug Administration (FDA) has approved Takeda Pharmaceuticals America Inc’s application for Orzeyful (oveporexton) tablets for the treatment of narcolepsy type 1 in adults, marking the first time a medicine has been approved to treat the condition as a complete disorder.

Orzeyful is the first drug to work by directly targeting the loss of orexin signaling, which causes the disease. Rather than masking symptoms with stimulants or sedatives, the twice-daily oral tablet activates the same brain receptor that the body’s own orexin would normally stimulate to restore the missing signal.

“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,” says Tiffany R Farchione, MD, director of the division of psychiatry within the FDA’s Center for Drug Evaluation and Research, in a release. “This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole.”

The effectiveness and safety of Orzeyful were evaluated in two randomized, double-blind, placebo-controlled 12-week studies enrolling 273 adults. Patients taking a 2 mg dose showed improvements in their ability to stay awake during the day compared with those receiving a placebo. Patients also reported substantially less daytime sleepiness, a significant reduction in cataplexy episodes, and meaningful improvement across the full spectrum of narcolepsy symptoms.

The most common side effects included insomnia, increased urinary frequency, urgency to urinate, and increased saliva production, though the rate of participants stopping treatment due to side effects was low. Orzeyful should not be used at the same time as strong CYP3A inhibitors. Its safety and effectiveness have not been established in patients under 18 years of age.

The drug received Breakthrough Therapy Designation and Priority Review from the FDA. Orzeyful has been recommended for scheduling under the Controlled Substances Act and will be lawful to market following a scheduling decision issued by the Drug Enforcement Agency.

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