#178 - Orexin Agonists Are Here: This Is The New Stuff Sleep Unplugged With Dr. Chris Winter podcast

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#178 - Orexin Agonists Are Here: This Is The New Stuff

4d ago 39:13

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The orexin receptor agonists are coming. After years of managing narcolepsy with stimulants, sodium oxybate, and wake-promoting agents, we soon will have medications that target the root cause of the disorder: the loss of orexin signaling. These new drugs—developed by Takeda, Alkermes, and Centessa—aren’t just incremental improvements. They represent a genuine shift in how we understand and treat hypersomnolence disorders. In this episode, we will:

Define what orexin is and why losing it destabilizes wakefulness, REM boundaries, muscle tone, and cognition
Learn how orexin agonists work—not as stimulants, but as replacement therapy for a missing neurotransmitter
Find out why OX2R is the key receptor, and how selective agonists restore stable wakefulness, reduce cataplexy, and normalize attention
Review the available clinical data from the new wave of programs: oveporexton (Takeda), alixorexton (Alkermes), and ORX750 (Centessa)
See what makes these drugs different from modafinil, amphetamines, solriamfetol, and oxybate therapies
Learn why Phase 1, Phase 2, and Phase 3 trials matter—with quick insights on how these drugs reached such strong results
Consider safety and side effects, including what Hy’s Law means and why regulators watch liver signals so closely
Look ahead to what these medications may mean for NT1, NT2, IH, and other hypersomnolence disorders in the coming years
Speculate why this class represents one of the most exciting moments in modern sleep medicine

Produced by: Maeve Winter
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