FDA approves first therapy targeting cause of narcolepsy type 1
Orzeyful is the first approved therapy to treat NT1 as a complete disorder
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The FDA has approved Orzeyful as the first therapy to target the underlying cause of narcolepsy type 1 in adults.
The U.S. Food and Drug Administration (FDA) has approved Takeda‘s oral therapy Orzeyful (oveporexton) for adults with narcolepsy type 1 (NT1).
“The FDA approval of ORZEYFUL marks a new chapter for the narcolepsy type 1 community, as we introduce an entirely new class of medicine that will potentially redefine how this disease is managed and how people feel on treatment,” Julie Kim, president and CEO of Takeda, said in a company press release.
Orzeyful targets the orexin loss underlying NT1
The approval makes Orzeyful the first and only FDA-approved therapy to target the underlying cause of NT1 and treat the condition as a whole, rather than addressing individual symptoms.
“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. This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole,” Tiffany R. Farchione, MD, director of the Division of Psychiatry within the FDA’s Center for Drug Evaluation and Research, said in a press release from the agency.
NT1 is caused by the loss of nerve cells in the brain that produce orexin, also called hypocretin. Orexin is a chemical messenger that helps regulate wakefulness, sleep and muscle tone. Its loss can cause excessive daytime sleepiness and cataplexy, a sudden loss of muscle tone.
Orzeyful is an agonist, or activator, of orexin receptor 2 (OX2R). By activating this receptor, the therapy restores the missing orexin signal associated with NT1. Orzeyful may be taken with or without food and is taken twice daily: one dose after awakening and a second dose three to five hours later.
“With this approval, we are turning scientific discovery into reality for adults living with narcolepsy type 1,” said Andy Plump, MD, PhD, Takeda’s president of research and development. “ORZEYFUL is just the beginning. With orexin emerging as a powerful therapeutic pathway, Takeda is unlocking the potential of this new class of medicine for patients across a range of disorders.”
Phase 3 trials support FDA approval in adults
FDA approval of Orzeyful for adults with NT1 comes less than a month after the therapy was approved in China to treat NT1 in people ages 16 and older. Both approvals were based mainly on data from two Phase 3 clinical trials, called FirstLight (NCT06470828) and RadiantLight (NCT06505031).
Both trials compared Orzeyful with a placebo over 12 weeks. Results showed that Orzeyful significantly improved wakefulness and reduced cataplexy attacks. Data from the trials also showed that Orzeyful improved daily functioning and patient-reported quality of life, eased cognitive symptoms, and improved nighttime sleep.
“Until now, people have managed narcolepsy type 1 with treatments that target symptom relief,” said Emmanuel Mignot, MD, PhD, principal U.S. investigator in the Orzeyful Phase 3 program. “As the first and only approved orexin therapy to treat the broad spectrum of the disease, ORZEYFUL can enable a different kind of conversation in the doctor’s office about treatment options.”
The most common side effects of Orzeyful include trouble sleeping (insomnia), urinary urgency, urinary frequency, and excessive salivation. The therapy should be avoided in patients with severe liver impairment or severe kidney impairment requiring dialysis, and it should not be used in combination with medications that strongly block the activity of an enzyme called CYP3A. Available data are insufficient to determine the risks of using Orzeyful during pregnancy; a registry will collect data on outcomes from pregnancies exposed to Orzeyful.
Draft prescribing information for Orzeyful also notes that the therapy has potential for abuse and misuse, and that abuse may lead to addiction. The U.S. Drug Enforcement Administration (DEA) is currently reviewing the therapy to determine its controlled substance classification. Once the DEA makes its determination, final prescribing information will be published and the therapy will be made commercially available through a specialty pharmacy. The classification is expected within 90 days, and updates are available on the newly approved therapy’s website.
“We are proud to have discovered and developed this orexin treatment innovation and will bring it to adults living with NT1 as quickly as possible,” Kim said.
Rachel Nesmith
So excited! Cannot wait to try.