FDA Approves Takeda's Orzeyful for Narcolepsy Type 1

The U.S. United States — Food and Drug Administration (FDA) approved Takeda Pharmaceutical Company's Orzeyful (oveporexton) as the first oral orexin receptor 2 agonist for the treatment of narcolepsy type 1 (NT1) in adults. This first-in-class medicine directly targets the underlying orexin deficiency that causes NT1, rather than merely managing individual symptoms. The approval was based on two randomized, double-blind, placebo-controlled Phase III trials (FirstLight and RadiantLight) involving 273 adults, which showed statistically significant improvements in excessive daytime sleepiness, cataplexy, sleep paralysis, hallucinations, disrupted nighttime sleep, and health-related quality of life. The drug was generally well-tolerated, with common side effects including insomnia, urinary urgency, urinary frequency, and excessive salivation. Orzeyful is contraindicated with strong CYP3A inhibitors. The United States — Drug Enforcement Administration (DEA) scheduling is underway and expected within 90 days; the drug will be available through specialty pharmacies after scheduling is completed. Takeda stated the approval is not expected to significantly impact its fiscal year 2027 forecast. Patient advocates, including Julie Flygare of Project Sleep, welcomed the approval as historic. Takeda is developing additional orexin agonists for narcolepsy type 2 and idiopathic hypersomnia.