A new generation of drugs could transform the lives of people affected by narcolepsy and form the basis of future treatments for other neuropsychiatric disorders, including ADHD and depression. The Food and Drug Administration has approved oveporexton (brand name Orzeyful), the first orexin-agonist treatment for narcolepsy.
But the “excitement is not just about narcolepsy,” said The Economist. Drugmakers are “betting” that orexins could “follow a similar path” to semaglutide (like Ozempic) and tirzepatide (like Mounjaro), the GLP-1 receptor agonists initially developed as diabetes medication before their wider applications were unlocked.
What are orexins? Peptides (chains of amino acids) produced in the brain carry messages between neurons relating to the body’s sleep-wake system, as well as reward and motivation. These cells seem to die off in people with narcolepsy type 1. This means their brains lose the “ability to control” when their body sleeps, said Time.
How do orexin agonists work? In 2011, researchers at Japanese pharmaceutical company Takeda found a chemical compound that turned the orexin receptor off and could therefore become a treatment for insomnia. But the “bigger prize may lie not in blocking orexin’s signal but restoring it,” said The Economist. Oveporexton, also developed by Takeda, “activates the orexin pathway” and “restores the brain’s ability to remain alert,” said Time.
Narcoleptic volunteers who took oveporexton in a clinical trial were able to stay awake up to 25 minutes longer than those who hadn’t taken it and also had fewer episodes of cataplexy, loss of muscle control, hallucinations and irregular sleep. “It was the first time I felt somewhat alive in the last 10 years,” said one 19-year-old trial participant to Nature. “It’s the best thing that has ever happened to me.”
What might the future hold? Around 1 in 2,000 people in the U.S. and Western Europe suffer from narcolepsy. Orexin-agonist-based medicines for narcolepsy and other sleep disorders could generate $15.9 billion a year by 2035, according to Morgan Stanley estimates.
And oveporexton’s success “opens the door to the use of orexin-mimicking drugs for other conditions associated with low levels of the chemical,” such as ADHD and depression, said Smithsonian Magazine. This is “just the beginning,” said Andy Plump, Takeda’s president of research and development to the outlet.
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