The Brain May Be About to Have Its Ozempic Moment (Economist)

Section: Science & technology · Edition: 2026-08-15 Edition · Print headline: "Wide awake"

Summary

The thesis is an analogy: GLP-1s showed what happens when a drug aims at an entire regulatory system (hunger) rather than a symptom; drugmakers are betting that the orexins, two hypothalamic neuropeptides that regulate wakefulness, are the next such system. The occasion is the FDA approval on 5 August 2026 of oveporexton (Takeda), the first orexin agonist, for narcolepsy. Narcolepsy is the beachhead; the hoped-for market is depression, ADHD, addiction and sleep apnoea. The article is clear that those wider uses are "hints, not proof".

The commercial picture

• Oveporexton (Takeda, Japan): first orexin agonist approved, 5 Aug 2026, for narcolepsy. Alkermes (Ireland) has a competitor in development.
• Eli Lilly bought Centessa, a biotech with an orexin agonist in early trials, in June 2026 in a deal worth up to $7.8bn depending on trial success (the Lilly platform piece quotes the headline figure; this article makes the contingency explicit).
• Morgan Stanley: orexin medicines could reach $16bn/yr by 2035 from narcolepsy and related sleep disorders alone, versus ~$3bn/yr for today's narcolepsy drugs.
• Narcolepsy afflicts roughly 1 in 2,000 Americans; depression, ADHD and addiction "burden hundreds of millions".

The science, briefly

• Orexins (also "hypocretins") were found in January 1998 by Luis de Lecea's team at Scripps and, weeks later, by Yanagisawa Masashi's team at UT Southwestern, who named them for appetite after rats injected with them ate more.
• 1999: Emmanuel Mignot (Stanford) showed hereditary narcolepsy in Dobermans and Labradors came from a mutation blocking the response to orexin; Yanagisawa's mice lacking orexin collapsed into sleep; narcoleptic humans turned out to have lost the orexin-producing neurons.
• Two receptors: OX2R sustains wakefulness by co-ordinating norepinephrine, serotonin, dopamine and other arousal systems ("the conductor of an orchestra"); OX1R is more involved in reward and motivation.
• Orexin antagonists (switching OX2R off) have treated insomnia since 2014 and, per Birgitte Kornum (Copenhagen), produce something closer to natural sleep than GABA-enhancing sleeping pills, which sedate and lose effect with use.
• Agonists are harder: the drug must reproduce the effect of a peptide many times its size and cross the blood–brain barrier. Takeda's first attempt, firazorexton, was discontinued in 2021 after liver damage in several patients.

The trial the article reports

• Oveporexton phase 2, published May 2025: 90 patients with narcolepsy type 1, eight weeks. Outcome: the Maintenance of Wakefulness test (sit in a darkened room, try to stay awake). Untreated, many fell asleep in about a minute; on the drug they stayed awake 12.5 to 25 minutes longer depending on dose, pushing many into the normal range. Cataplexy attacks were roughly a third as frequent as on placebo. Side-effects: insomnia and, in about a third of patients, an uncomfortable urge to urinate.
• Lilly/Centessa agonist, early trial of 55 patients: wakefulness improved by >20 minutes in NT1 and >10 minutes in NT2. The article calls the sample small and the data preliminary.
• Mechanistic claim (Yanagisawa): because orexin acts upstream and co-ordinates the arousal systems rather than flooding dopamine and norepinephrine everywhere (as methylphenidate and modafinil do), agonists should give more natural, stable wakefulness with fewer side-effects and less abuse potential than stimulants. That is a hypothesis, not a trial result.

What is flagged as unproven

• Every use beyond narcolepsy. ADHD (Alkermes trial in adults, on the observation that narcolepsy patients report sharper attention; current ADHD drugs are already "pretty effective"). Sleep apnoea (being explored). Addiction (blocking OX1R "shows promise" for cravings). Depression and motivation via activating OX1R: the most speculative idea in the piece, offered by Yanagisawa as a belief.
• Whether the stimulant comparison (fewer side-effects, less abuse) holds in practice: the phase 2 trial was eight weeks in 90 people.
• Dan Skovronsky (Lilly chief scientific officer) supplies the analogy's logic: hunger and sleep are both "master homeostasis mechanisms". The article presents this as the drug industry's hope, not an established result.

Connects to

• GLP-1s — the analogy's source; updated with a brain/neuro section citing this page
• Eli Lilly — Centessa acquisition; "does not intend to miss another peptide boom"
• Eli Lilly Is Reinventing the Pharma Business (Economist) — Skovronsky's earlier remark that sleep-regulating drugs may have benefits "just as broad as those of GLP-1s" is the same thesis a month earlier
• Dementia Prevention — the other brain-health thread in this batch; both are about acting on systems rather than symptoms
• Mental Health Access (China) — the demand side: depression and anxiety at population scale with thin treatment capacity