Where narcolepsy treatment is heading

Narcolepsy causes overwhelming daytime sleepiness, and in type 1, sudden muscle weakness triggered by emotion (cataplexy). It affects roughly 1 in 2,000 people. Type 1 is caused by the loss of brain cells that make orexin, a wakefulness signal; until 2026, every treatment only managed symptoms. The first drug that replaces the missing signal itself was just approved.

• 42studies open or running
• 11phase 3 trials
• 303papers published this year
• 31NIH-funded projects

1. Now

   Nov 2026

   First drug that treats the underlying causeHappened +19.8 min more wakefulness

   Oveporexton restored up to 19.8 more minutes of wakefulness on a standard test and cut cataplexy by up to 89%.

   +19.8 min: more time staying awake on a standard sleepiness test.

   • FirstLight and RadiantLight trials

   An existing drug's side benefitHappened 26% lost 5%+ of body weight

   Low-sodium oxybate also helped many overweight patients lose weight.

   26%: of people lost 5% or more of their body weight.

   • Low-sodium oxybate weight study

2. 6 months

   by May 2027

   A rival orexin agonist in late-stage testingPossible

   Alkermes's ALKS 2680 is in two phase 3 trials, one for each narcolepsy type; due May 2027.

   • Brilliance NT1
   • Brilliance NT2

3. 12 months

   by Nov 2027

   Extending orexin drugs to narcolepsy type 2Possible

   Takeda's TAK-360, a second-generation orexin agonist, is being tested in people without cataplexy, who don't fully lack orexin; due June 2031.

   • TAK-360 trial

4. 3 years

   by late 2029

   More companies entering the orexin racePossible

   Harmony Biosciences's HBS-301 and Centessa's cleminorexton both begin phase 3 testing; due 2027.

   • HBS-301 trial
   • Cleminorexton trial

   A non-orexin pill in phase 3Long shot

   Samelisant, which works through a different brain pathway (histamine H3), is being tested as an alternative; due November 2027.

   • Samelisant trial

5. 5 years

   by late 2031

   Whether orexin drugs help without orexin lossLong shot

   Results in narcolepsy type 2 and idiopathic hypersomnia, where orexin cells are not lost the same way, will show how far this drug class can reach.

   • Brilliance NT2

The research paths

Open to join now

• Narcolepsy

  HBS-301

  Phase 3 · 64 sites

  Locations and eligibility →

• Central hypersomnia conditions

  TAK-861 (oveporexton) in related sleep conditions

  Phase 3 · 52 sites

  Locations and eligibility →

• Narcolepsy and idiopathic hypersomnia

  ALKS 2680 long-term study

  Phase 3 · 50 sites

  Locations and eligibility →

• Narcolepsy type 2

  ALKS 2680 (Brilliance NT2)

  Phase 3 · 44 sites

  Locations and eligibility →

• Narcolepsy type 1

  ALKS 2680 (Brilliance NT1)

  Phase 3 · 44 sites

  Locations and eligibility →

• Narcolepsy or idiopathic hypersomnia

  TAK-360

  Phase 3 · 33 sites

  Locations and eligibility →

• Narcolepsy

  Cleminorexton

  Phase 3 · 26 sites

  Locations and eligibility →

• Narcolepsy

  Xywav expanded dosing (XYRISE)

  Phase 3 · 15 sites

  Locations and eligibility →

• Narcolepsy

  Samelisant

  Phase 3 · 1 site

  Locations and eligibility →

See every recruiting Narcolepsy trial →

When the trials finish

Completion dates the trials registered. Results usually follow 3 to 12 months later.

What just happened

Standard treatment today

• Narcolepsy type 1Oveporexton, or stimulants/wake-promoting pills plus an anticataplectic drug (oxybate, venlafaxine).
• Narcolepsy type 2Stimulants or wake-promoting pills (modafinil, solriamfetol, pitolisant); oxybate if needed.
• Idiopathic hypersomniaSimilar wake-promoting drugs; low-sodium oxybate is approved for this too.

See Narcolepsy trials recruiting now →