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# Takeda Sets the Benchmark for a New Class of Sleep-Wake Medicines
- URL: https://biopharmabrief.com/takeda-sets-the-benchmark-for-a-new-class-of-sleep-wake-medicines/
- Published: 2026-09-08T22:51:35.000Z
- Updated: 2026-09-08T22:51:35.000Z
- Author: Logan Mavar

*Takeda secured the first U.S. approval. Alkermes and Lilly are testing how far orexin receptor agonists can extend beyond narcolepsy type 1.*

Takeda’s Orzeyful recently became the [first orexin receptor agonist approved in the United States](https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-narcolepsy/?ref=biopharmabrief.com) for narcolepsy type 1, introducing a treatment that directly targets the biological pathway disrupted by the disease.

Narcolepsy type 1 is caused by the [loss of neurons that produce orexin](https://www.takeda.com/newsroom/newsreleases/2025/positive-results-phase-3-oveporexton-narcolepsy-type-1/?ref=biopharmabrief.com), a signaling molecule that helps the brain maintain wakefulness. The resulting loss of orexin signaling can cause excessive daytime sleepiness, disrupted nighttime sleep and cataplexy, a sudden loss of muscle control. Orzeyful [activates orexin receptor 2](https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-narcolepsy/?ref=biopharmabrief.com), restoring signaling through the pathway and improving several symptoms through a single mechanism.

Orzeyful’s first-in-class approval gives Takeda time in the market before competing orexin agonists arrive. Alkermes is [advancing alixorexton through Phase 3](https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-initiation-phase-3-brilliance-studies?ref=biopharmabrief.com), while Lilly has [acquired a pipeline](https://investor.lilly.com/news-releases/news-release-details/lilly-completes-acquisition-centessa-pharmaceuticals-advance?ref=biopharmabrief.com) spanning several sleep-wake disorders. Their programs could compete with Orzeyful in narcolepsy type 1 while extending the class into conditions where severe orexin deficiency is not the defining biology.

## Orzeyful Establishes the Benchmark

Orzeyful’s approval was supported by [two Phase 3 trials](https://www.takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/?ref=biopharmabrief.com) that showed improvements across wakefulness, cataplexy, daily function and quality of life.

At the higher approved dose of 2 milligrams twice daily, most [participants achieved wakefulness](https://www.takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/?ref=biopharmabrief.com) within the normal range on the Maintenance of Wakefulness Test, and nearly 85% reported daytime sleepiness scores comparable to those of healthy individuals. Across doses, median weekly cataplexy rates fell by more than 80% from baseline.

Orzeyful was generally well tolerated. Takeda reported [no serious treatment-related adverse events](https://www.takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/?ref=biopharmabrief.com) in the pivotal trials, although insomnia, urinary frequency and urinary urgency were common. Those effects leave room for competing drugs to differentiate through tolerability as well as dosing and clinical performance.

Takeda expects to make Orzeyful available after the [Drug Enforcement Administration completes its scheduling process](https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-narcolepsy/?ref=biopharmabrief.com). The company is also developing [TAK-360](https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-japan-narcolepsy/?ref=biopharmabrief.com), another oral orexin receptor 2 agonist, across narcolepsy types 1 and 2 and idiopathic hypersomnia.

## Alkermes Pushes Beyond Orexin Deficiency

Alkermes is developing alixorexton for narcolepsy types 1 and 2\. The drug improved wakefulness and daytime sleepiness in Phase 2 trials, including in [type 2 patients who do not typically have severe orexin deficiency](https://investor.alkermes.com/news-releases/news-release-details/alkermes-presents-detailed-positive-results-vibrance-2-phase-2/?ref=biopharmabrief.com).

[Three Phase 3 trials](https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-initiation-phase-3-brilliance-studies?ref=biopharmabrief.com) are testing once-daily and split-dose regimens. A successful once-daily regimen could offer a dosing advantage over twice-daily Orzeyful, while approval in type 2 would expand the mechanism into a new patient population.

Alkermes is also [testing alixorexton in Phase 2](https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-initiation-phase-3-brilliance-studies?ref=biopharmabrief.com) for idiopathic hypersomnia, providing another test of the mechanism in patients without known orexin deficiency.

## Lilly Pursues a Best-in-Class Profile

Lilly [completed its acquisition of Centessa](https://investor.lilly.com/news-releases/news-release-details/lilly-completes-acquisition-centessa-pharmaceuticals-advance?ref=biopharmabrief.com) in June after agreeing to pay approximately [$6.3 billion upfront](https://investor.lilly.com/node/54066?ref=biopharmabrief.com), gaining an orexin pipeline led by cleminorexton.

Lilly describes cleminorexton as a potential [best-in-class candidate](https://investor.lilly.com/node/54066?ref=biopharmabrief.com) based on Phase 2a studies across narcolepsy types 1 and 2 and idiopathic hypersomnia. The program still trails Orzeyful and alixorexton in development.

The acquisition also added [clinical and preclinical orexin agonists](https://investor.lilly.com/node/54066?ref=biopharmabrief.com) with potential applications across neurological, neurodegenerative and neuropsychiatric conditions. Those programs could extend Lilly’s orexin pipeline beyond sleep-wake disorders.

## **The Orexin Market Takes Shape**

Orzeyful gives Takeda the first approved drug in the class and establishes the benchmark for treating narcolepsy type 1\. Alixorexton and cleminorexton will need to compete on dosing, tolerability, clinical performance and access. A once-daily regimen or better tolerability could give either drug room to differentiate despite Orzeyful’s first-mover advantage.

The opportunity extends beyond competing for the same patients. Alkermes is testing alixorexton in narcolepsy type 2 and idiopathic hypersomnia, while Lilly gained a broader pipeline of orexin agonists through its acquisition of Centessa. Success in those programs could expand orexin receptor agonism to disorders in which severe orexin deficiency is not the defining biology.

Takeda has established that the mechanism works in narcolepsy type 1\. The next results will determine who can compete with Orzeyful and how much larger the orexin agonist class can become.