The U.S. Food and Drug Administration has approved Orzeyful (oveporexton), an oral tablet that treats narcolepsy type 1 in adults by going after the disorder’s biological cause rather than merely soothing its symptoms.
The drug is a first in two respects. It is the first medicine licensed for narcolepsy type 1 as a single, whole disorder rather than symptom by symptom, and the first to act directly on the loss of orexin signaling that gives rise to the illness. Orexin, sometimes called hypocretin, is a messenger molecule the brain relies on to stay alert and to police the boundary between sleep and wakefulness. In narcolepsy type 1, the neurons that produce it die off, so the signal never reaches the brain. Orzeyful compensates by switching on the same receptor orexin would normally activate, effectively restoring the missing command. It is taken twice a day.
Until now, patients leaned on stimulants and sedatives that masked individual complaints. The underlying disease is a rare, lifelong condition thought to affect about 1 in 2,000 people in the United States. Its hallmark is overwhelming daytime sleepiness, often paired with cataplexy — sudden muscle weakness triggered by strong emotions such as laughter — along with sleep paralysis, hallucinations while falling asleep or waking, and sleep that is constantly broken at night.
“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.”
The approval rests on two randomized, double-blind, placebo-controlled trials, each lasting 12 weeks, that enrolled 273 adults with the condition. In both studies, participants given Orzeyful 2 mg stayed awake longer during the day than those on placebo, reported considerably less daytime drowsiness, and experienced markedly fewer cataplexy episodes, with gains spanning the rest of the symptom spectrum as well.
The most common side effects were insomnia, urinating more often and with greater urgency, and increased saliva production; few patients dropped out of the studies because of them. Orzeyful should not be combined with strong CYP3A inhibitors, and its safety and effectiveness in people under 18 have not been established. The FDA has recommended the drug for scheduling under the Controlled Substances Act, and it cannot be marketed until the Drug Enforcement Administration issues its scheduling decision.
Orzeyful earned Breakthrough Therapy designation, which speeds FDA guidance for medicines with early evidence of major gains over existing options for serious conditions, and Priority Review, a fast-track assessment for treatments expected to make a meaningful difference. The license went to Takeda Pharmaceuticals America, Inc.
Source: FDA Press Announcement
