Takeda and Alkermes Detail Strong Clinical Results for Orexin Drugs in Narcolepsy – Head-to-Head Race Accelerates

Takeda’s orexin receptor 2 agonist, oveporexton (TAK-861), showed statistically significant improvements in all symptoms of narcolepsy type 1 (NT1) in two Phase 3 randomized, double-blind, placebo-controlled studies, including excessive daytime sleepiness, cataplexy, attention, and quality of life24.

Nearly 85% of participants on high-dose oveporexton achieved self-reported sleepiness scores comparable to healthy individuals, and the average number of cataplexy-free days per week increased from zero at baseline to four or five days by week 12, with placebo showing no such increase1.

Oveporexton was generally well tolerated; the most common side effects were urinary frequency/urgency and insomnia, which typically resolved within one week. No liver toxicity was reported, an improvement over Takeda’s previous orexin agonist efforts12.

In two 12-week Phase 3 trials, high-dose oveporexton increased average wakefulness by 17 to 20 minutes more than placebo as measured by the Maintenance of Wakefulness Test (MWT), with patients reaching 22 to 25 minutes (normal wakefulness threshold is 20 minutes)3.

Alkermes’ orexin agonist, alixorexton, achieved statistically significant improvements in a six-week Phase 2 trial, increasing wakefulness by 26 minutes more than placebo, reaching 28 minutes at study end—also exceeding the normal wakefulness threshold3.

Alixorexton offers once-daily dosing and a strong alertness profile, but some patients experienced blurred vision as a side effect, typically resolving within three days. Urinary frequency/urgency and insomnia were also reported, similarly transient1.

Both drugs directly target the underlying orexin deficiency in NT1, representing a new therapeutic class likely to transform the standard of care; Takeda appears poised to reach the market first, but Alkermes’ program is advancing rapidly1235.

Sources:

1. https://medcitynews.com/2025/09/takeda-is-waking-up-the-narcolepsy-market-with-first-in-class-drug-but-alkermes-is-on-its-heels/

2. https://www.takeda.com/newsroom/newsreleases/2025/positive-results-phase-3-oveporexton-narcolepsy-type-1/

3. https://www.statnews.com/2025/09/08/alkermes-takeda-narcolepsy-sleep-medicines/

4. https://www.biospace.com/drug-development/takeda-establishes-lead-in-narcolepsy-race-with-back-to-back-phase-iii-wins

5. https://www.fiercebiotech.com/biotech/takeda-alkermes-lift-lid-rival-narcolepsy-hopefuls-race-fda-heats