FDA Approves Takeda's Orzeyful, First US Orexin Drug for Narcolepsy Type 1
The twice-daily oveporexton tablet activates the orexin receptor 2; it will reach patients after the DEA decides how to schedule it, which Takeda expects within 90 days.
The FDA approved this drug or biologic for a specific use.
Key points
- The FDA approved Takeda's Orzeyful (oveporexton) on August 5 for adults with narcolepsy type 1, calling it the first drug to work by directly targeting the loss of orexin signaling.
- Approval was based on two Phase 3, placebo-controlled 12-week studies, FirstLight and RadiantLight, in 273 adults; insomnia and urinary frequency were the most common side effects.
- The drug had breakthrough therapy designation and priority review; it can be marketed once the Drug Enforcement Administration completes its scheduling decision.
The US Food and Drug Administration approved Takeda's Orzeyful (oveporexton) tablets for adults with narcolepsy type 1 (NT1), the agency announced on August 5. The FDA said Orzeyful is the first medicine approved for narcolepsy type 1 as a complete disorder and the first to work by directly targeting the loss of orexin signaling that causes the disease.
Narcolepsy type 1 is caused by the loss of brain cells that produce orexin, a chemical messenger that regulates wakefulness, sleep and muscle tone, according to the FDA. Its symptoms include excessive daytime sleepiness, cataplexy (sudden muscle weakness triggered by strong emotions), sleep paralysis, hallucinations and disrupted nighttime sleep. The FDA estimates it affects about 1 in 2,000 people in the US; Takeda puts the figure at about 120,000 people.
Oveporexton is an oral orexin receptor 2 (OX2R) agonist, taken twice daily, that activates the receptor the body's own orexin would normally stimulate.
The evidence
The FDA said effectiveness and safety were evaluated in two randomised, double-blind, placebo-controlled 12-week studies enrolling 273 adults with NT1. Takeda identifies them as the global Phase 3 FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) studies. Across both, patients on the 2 mg dose showed improvements in their ability to stay awake during the day compared with placebo, and reported less daytime sleepiness and a significant reduction in cataplexy episodes, according to the agency.
The most common side effects were insomnia, increased urinary frequency, urinary urgency and increased saliva production. In pooled Phase 3 data cited by Takeda, insomnia occurred in 60% of patients on 2 mg twice daily, 55% on 1 mg twice daily and 1% on placebo, and urinary frequency in 58%, 53% and 5%. The drug is not to be used with strong CYP3A inhibitors, and its safety and effectiveness have not been established in people under 18.
"This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole," said Tiffany R. Farchione, director of the Division of Psychiatry in the FDA's Center for Drug Evaluation and Research.
Scheduling and launch
Orzeyful received breakthrough therapy designation and priority review. It has been recommended for scheduling under the Controlled Substances Act and can be marketed once the Drug Enforcement Administration issues its scheduling decision, the FDA said. Takeda said it expects that decision within 90 days, after which the drug will be distributed through a specialty pharmacy.
Takeda said the approval is not expected to have a significant impact on its consolidated financial forecast for the fiscal year ending March 31, 2027. The drug has also been approved in China, and the company is studying other oral orexin agonists, including TAK-360 for NT1, narcolepsy type 2 and idiopathic hypersomnia.
Sources
- FDA Approves First Drug to Treat the Full Range of Narcolepsy Type 1 Symptoms, US Food and Drug Administration, August 5, 2026
- U.S. FDA Approves Takeda's ORZEYFUL (oveporexton), the First and Only Medicine to Treat the Underlying Cause of Narcolepsy Type 1, Takeda, August 5, 2026