Feeling drowsy or tired and even falling asleep during the day may be part of our increasingly sleep-deprived culture, but these are also symptoms of a medical condition called narcolepsy. About 200,000 people in the U.S. and 3 million worldwide have the condition, and the symptoms can range from feeling tired during the day to suddenly and unexpectedly falling asleep and losing muscle control. There’s no cure for narcolepsy, and doctors generally treat it with stimulant drugs or amphetamines as well as behavior changes like scheduled naps to control the sleepiness episodes.
But now there’s a drug that addresses one of the biological mechanisms involved in narcolepsy. Food and Drug Administration approved Orzeyful, or oveporexton, which targets the orexin pathway that orchestrates the brain’s sleeping and wake cycles. Without orexin, the brain loses the ability to control when the body sleeps and when it’s awake.
Orzeyful is especially effective for disrupted sleep in narcolepsy type 1, which can be riskier because people lose muscle control and can injure themselves when they do. The drug activates the orexin pathway that is dysfunctional in people with the condition, restoring the brain’s ability to remain alert during the day, and is approved for people with narcolepsy type 1. Based on two studies submitted by Takeda, which developed the drug, involving more than 270 people with the condition, people taking the drug, which comes in pill form, twice a day, were better able to stay awake during the day than those taking a placebo.
They also had fewer episodes of cataplexy, or losing muscle control, as well as other symptoms such as irregular nighttime sleep and hallucinations. Because patients feel better on Orzeyful, the drug is now being reviewed by the Drug Enforcement Administration (DEA) for any addictive potential, and Takeda CEO and president Julie Kim tells TIME she expects it to receive a schedule IV designation, which indicates a low chance of dependence or abuse. Orzeyful has taken 15 years to develop, and included some failures along the way, says Kim.
The first versions of a drug that stimulated the orexin pathway simply weren’t practical, since they required receiving the medication through a continuous IV to keep orexin at proper levels. The first version of a pill form looked promising in early human testing, but lab tests showed abnormal effects on the liver, and although people in a study did not experience any negative side effects, the company decided to stop development of that drug. That decision might have been easier because the company was already testing another compound in parallel—Orzeyful—which turned out to be safer.
The success with Orzeyful in regulating the orexin pathway could lead to treatments for other, more common sleep disorders. Already, Takeda scientists are studying another orexin-based drug for narcolepsy type 2 and idiopathic hypersomnia, or excessive sleepiness even after a full night’s sleep. We are going to follow the science and look at designing molecules to fit different purposes.”
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