The FDA has approved oveporexton (Orzeyful; Takeda Pharmaceuticals) tablets for the treatment of patients with narcolepsy type 1 (NT1), marking the first medicine to address the condition as a complete disorder and the first to work by directly targeting the loss of orexin signaling that drives the disease.
A First-in-Class Mechanism
Narcolepsy type 1 is a rare, lifelong neuropsychiatric sleep disorder that affects an estimated 1 in 2000 people in the United States.
It is caused by the loss of brain cells that produce orexin, a chemical messenger that regulates wakefulness, sleep, and muscle tone.
The deficit produces a cluster of disabling symptoms, including excessive daytime sleepiness, cataplexy (sudden muscle weakness triggered by strong emotions such as laughter), sleep paralysis, hallucinations at the edge of sleep or waking, and disrupted nighttime sleep.
Efficacy Across the Symptom Spectrum
Approval was supported by the phase 3 FirstLight and RadiantLight trials, which were global, multicenter, placebo-controlled studies conducted across 19 countries that collectively enrolled 273 adults with NT1 over 12 weeks.
Patients taking oveporexton 2 mg showed improvements in their ability to stay awake during the day compared with placebo, along with substantially less daytime sleepiness, a significant reduction in cataplexy episodes, and meaningful improvement across the full spectrum of symptoms.
Oveporexton is an oral orexin receptor 2-selective agonist.
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Rather than masking symptoms with stimulants or sedatives, it selectively stimulates the same receptor the body’s own orexin would normally activate, restoring the missing signal to promote wakefulness and reduce abnormal rapid eye movement (REM)-sleep phenomena, including cataplexy.
Safety and Dispensing Considerations
The most common adverse effects were insomnia, increased urinary frequency, urgency to urinate, and increased saliva production.
The rate of participants stopping treatment because of adverse effects was low, and more than 95% of those who completed the trials enrolled in the ongoing long-term extension.
Pharmacists should counsel patients to report all medicines they are taking, as oveporexton should not be used at the same time as strong CYP3A inhibitors.
Oveporexton has been recommended for scheduling under the Controlled Substances Act, which will determine the record-keeping and dispensing requirements for the medication.
More information about oveporexton can be found on the FDA website.
Takeda Pharmaceuticals is the manufacturer.
