# Narcolepsy & excessive sleepiness
[Home](../README.md) · [Sleep](../WATCHLIST.md#sleep-health) · [Calendar](../MILESTONES.md)
Tags: [Drugs and biologics](../BROWSE.md#drugs)
## Current state
Orexin agonists and established wake-promoting treatments remain diagnosis-specific. A newly public 20-person ofatumumab NT1 protocol explores an immune approach without a comparator; one-month symptoms and one-week safety cannot establish durable benefit.
Status: active. Topic ID: `sleep_hypersomnolence`.
## Questions to follow
- Keep narcolepsy types 1 and 2, idiopathic hypersomnia and ordinary tiredness separate; retain diagnosis-specific trial populations and cataplexy outcomes.
- Follow objective daytime wakefulness, subjective sleepiness, function, quality of life and safety, including treatment-emergent insomnia.
- Verify announced approval, DEA scheduling and actual U.S. launch separately; do not treat a forecast as confirmed availability.
## Programs and next milestones
### Focused update — 2026-10-16
No additional finding was selected from these checked sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion.
**Remaining gaps:** Read current canonical scope, shared summaries, state and assigned topic notes. Bounded registry discovery covered July 18–October 16, 2026; prior October 13 findings were deduplicated. Full-topic successful-check dates remain unchanged.; Retrieved all 27 records across 1 pages of the bounded ClinicalTrials.gov query, plus 8 named records. Selected relevant new/changed protocols were appraised; downloading all records does not establish exhaustive safety/results review.; Europe PMC original-literature discovery failed with HTTP 503 for this topic. Targeted primary-source web searches supplied a partial fallback. Worldwide literature, regulators, international registries and complete original conference/podcast recordings remain incomplete.; The new condition baseline remains incomplete. Preceding 90-day registry discovery and selected inherited pivotal context were checked; the full older clinical, label and behavioral/device evidence corpus has not been completed.; TAK-360, orexin agonist and ofatumumab records refreshed; the selected original patient account is informal only. Existing Orzeyful approval remains separate from conditional availability; no verified DEA scheduling/actual launch was found. Full labels, extensions, rare harms and original audio remain incomplete.
**Informal-source coverage:** Read original TAK-360/Kyra thread and selected one explicitly unconfirmed dose/sleep account, preserving unknown exact posting date. Original comment permalink separate fetch failed but text is visible in the parent thread. No formal clinical safety rate or approval/availability claim follows. Wider talks/podcasts remain incomplete.
[Full coverage record](../updates/2026-10-16_scheduled_research_update.md).
### Focused update — 2026-10-13
#### Ofatumumab enters a small uncontrolled narcolepsy-type1 trial
**Newly public protocol — NCT07871006, first posted October 13.** Xijing Hospital, Xi’an plans **20 people aged 10–60 with treatment-refractory narcolepsy type 1** in an open-label single-group Phase 1/2 study of one **20 mg subcutaneous ofatumumab** dose. Primary measures are **Epworth Sleepiness Scale and cataplexy frequency at one month**; adverse events are listed over one week.
Ofatumumab is a CD20-directed B-cell-depleting antibody, a different approach from restoring orexin signaling with an agonist. With no concurrent comparator, the protocol cannot establish superiority, remission/cure, restoration of orexin neurons or durable safety. Particularly brief registered safety endpoints do not exclude later infection/immune harms; the established MS label warns about infections, injection/hypersensitivity reactions, reduced immunoglobulins and liver injury.
The registry says **recruiting**, actual start **October 1, 2025**, estimated primary completion **June 30, 2027**, final **December 31, 2027**. Thus October 13 is registration disclosure, not verified first dosing. No results. Existing U.S. Kesimpta approval is for **adult relapsing MS**, not narcolepsy or this pediatric exposure.
**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07871006); [Source 2](https://www.novartis.com/us-en/sites/novartis_us/files/kesimpta.pdf).
**Remaining gaps:** Read current canonical scope, shared summaries/state and assigned topic notes. September 5–October 13 overlap preserves the September 12 full-review dates; October 6/9 entries were deduplicated. All pages of each bounded ClinicalTrials.gov query were downloaded, and named records plus selected relevant new/changed protocols were appraised. This is focused partial review, not a worldwide full literature/regulator/safety census; successful full-topic dates must remain unchanged.; Bounded query retrieved 15 records across 1 pages; incidental studies excluded. Named topic records refreshed: 7. Full older evidence, international registries, comprehensive harms and all original conference/podcast recordings remain gaps.; New condition-specific baseline remains incomplete. Selected inherited older pivotal sources and newly recovered formal programs were reviewed, without declaring the preceding 90-day/older trial corpus complete.
**Informal-source coverage:** Revisited original narcolepsy threads on expected Orzeyful availability and trial experiences; November forecast remains conditional and no official DEA action found. The older August 24 alixorexton paper is not new October news. No new verified availability or attributable development rumor selected; full talk/audio incomplete.
[Full coverage record](../updates/2026-10-13_scheduled_research_update.md).
### Focused update — 2026-10-09
#### XYRISE studies expanded Xywav dosing in narcolepsy and idiopathic hypersomnia
**Baseline context, XYRISE / NCT07625280, JZP258-304.** Jazz plans **120 adults with narcolepsy or idiopathic hypersomnia** in a masked placebo-controlled randomized-withdrawal study of expanded Xywav regimens. Narcolepsy and IH cohorts each include once- and twice-nightly regimens.
Participants receive open-label medication for up to 14 weeks to reach a stable dose, then continue that dose or switch to placebo for two weeks. Primary is **Epworth Sleepiness Scale change between stabilization and the withdrawal period**, not a polysomnographic sleep-architecture endpoint. This enrichment/design limits generalization to unselected patients and comparison with orexin agonists. Exact expanded dose ceilings are not supplied in the public arm descriptions; do not invent them.
The October 8 record says **recruiting**, actual start **July 9, 2026**; no results. Existing approved Xywav uses do not establish approval for each expanded regimen. Estimated primary completion **December 23, 2027** and final **January 6, 2028** are not public-result promises.
**Sources:** [Primary source 1](https://clinicaltrials.gov/study/NCT07625280).
**Remaining gaps:** New condition baseline remains incomplete. Reviewed inherited hub, preceding 90-day development leads and selected older pivotal/contextual sources; October 6 findings deduplicated.; 93 named NCT records across the ten topics and ten discovery queries downloaded successfully through the ClinicalTrials.gov public API. Download is not a claim that all fields/safety/results were exhaustively appraised.; Focused review only. Do not advance full successful-check timestamps or label incomplete remaining searches as no news.; All 13 matches in the bounded hypersomnolence discovery downloaded; selected relevant records screened. Saved orexin protocols refreshed. Established oxybate/stimulant/pitolisant/solriamfetol full labeling/safety and whole-world baseline remain incomplete.; Official Orzeyful page retains expected-by-November availability conditional on DEA scheduling. No completed official DEA scheduling action established; do not imply launch.
**Informal-source coverage:** Original Oct7 r/Narcolepsy thread contains anonymous patient participation in an orexin trial, not a new official recruitment/readout milestone. Sponsor conditional Orzeyful forecast checked; full talk/audio not reviewed.
[Full coverage record](../updates/2026-10-09_scheduled_research_update.md).
### Focused update — 2026-10-06
#### Cleminorexton SAPPHIRE adds an orexin-agonist development baseline
**Historical baseline addition reviewed October 6, 2026.** Cleminorexton / ORX750 adds another orexin-2 agonist program. SAPPHIRE (NCT07598708) is a recruiting randomized quadruple-masked phase 2/3 trial, 222 planned adults with narcolepsy types 1/2, comparing two doses with placebo. Primary: Maintenance of Wakefulness Test change at week 12. Actual start May 29, 2026; September 30, 2027 primary and December 31 final completion are estimates. The protocol may later add idiopathic hypersomnia by amendment; it is not currently an established included cohort.
CRYSTAL-1 (NCT06752668), 248 planned participants, also includes idiopathic hypersomnia, has primary safety measures through day35 and secondary MWT/ESS through day28. Its April record remains recruiting with December2026 estimated completion. No registry results are posted. These older programs are new-to-watch baseline, not October starts or approvals. Current trial eligibility does not establish long-term efficacy/safety; urinary and insomnia effects require full published/sponsor appraisal.
[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT07598708) · [Source 2](https://clinicaltrials.gov/study/NCT07598708) · [Source 3](https://clinicaltrials.gov/api/v2/studies/NCT06752668) · [Source 4](https://clinicaltrials.gov/study/NCT06752668)
#### TAK-360 adds separate NT2 and idiopathic-hypersomnia trial baselines
**Historical baseline addition reviewed October 6, 2026.** TAK-360 is separate from approved oveporexton/TAK-861. Recruiting randomized placebo-controlled phase 2 trials enroll 88 planned narcolepsy-type-2 adults (NCT06952699) and 96 with idiopathic hypersomnia (NCT06812078). Both use four weeks of treatment; safety is primary and diagnosis-specific sleepiness/wakefulness or IH severity is secondary. November 30, 2026 primary/final completion is estimated, not an announced public result. The recruiting open-label extension NCT07646678 plans 500 prior-study participants and safety monitoring through up to five years; estimated completion June 15, 2031.
No results are posted and no U.S. marketing approval is established. Extension enrollment is selected and lacks a blinded comparator. Preserve separate NT2/IH populations, TAK aliases and the difference between measured wakefulness, symptom/function and long-term safety.
[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT06952699) · [Source 2](https://clinicaltrials.gov/study/NCT06952699) · [Source 3](https://clinicaltrials.gov/api/v2/studies/NCT06812078) · [Source 4](https://clinicaltrials.gov/study/NCT06812078) · [Source 5](https://clinicaltrials.gov/api/v2/studies/NCT07646678) · [Source 6](https://clinicaltrials.gov/study/NCT07646678)
**Coverage:** 2026-10-06: narcolepsy orexin agonist SeptemberOctober2026 Centessa ORX750 TAK360; registry query30latest; 2026-10-06: cleminorexton SAPPHIRE direct NCT07598708; 2026-10-06: oveporexton DEA FederalRegister scheduling and official product page; 2026-10-06: original Orzeyful waiting room RedditSep24
**Remaining gaps:** Pending condition baseline partially expanded with cleminorexton aliases/SAPPHIRE/CRYSTAL1, TAK360 and direct alixorexton/Vibrance3 status. Sources cover earlier90days and older pivotal context selectively.; Orzeyful sponsor page still says expected byNovember pendingDEA; final official DEA action not established. Established oxybate/stimulant/solriamfetol/pitolisant full label and new-program safety census incomplete. Centessa annual-report PDF exceeded webtool size; no numerical new efficacy/safety claims drawn from it.
**Informal-source coverage:** Sep24 r/Narcolepsy thread by Dobby_1235 repeats November forecast; a Requiredmetrics comment describes local TAK360 trial eligibility, not evidence of a new milestone. Exact comment times are not reliable from relative rendered labels; source original indexedSep24. Anecdotes are not efficacy or safety rates. Full conference/podcast recordings incomplete.
[Full coverage record](../updates/2026-10-06_scheduled_research_update.md).
### Oveporexton / Orzeyful — Takeda
**Development / U.S. status:** FDA approval was announced August 5, 2026, for adult narcolepsy type 1. The approval letter makes statutory approval and marketing dependent on DEA scheduling. The earlier product-source checks forecast availability by November 2026; completed scheduling and launch were not verified.
**Evidence / limitations:** FirstLight and RadiantLight had 168 and 105 participants and 12 weeks of controlled follow-up. FirstLight placebo-adjusted Maintenance of Wakefulness Test changes were 13.8 and 17.2 additional minutes. Insomnia and urinary symptoms were frequent; brief trials do not establish long-term safety.
**Next milestone:** Scheduling and verified launch; November remains a conditional sponsor forecast. [Approval letter](https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/220860Orig1s000ltr.pdf) · [FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220860Orig1s000lbl.pdf) · [Product forecast](https://www.orzeyful.com/) · [Full inherited baseline](12_sleep.md#sleep-hypersomnolence-baseline).
### Alixorexton / ALKS 2680 — Alkermes
**Development / U.S. status:** Investigational orexin-2 receptor agonist. Brilliance phase 3 studies address narcolepsy types 1 and 2; Vibrance 3 phase 2 addresses idiopathic hypersomnia. These indications remain separate.
**Evidence / limitations:** Earlier Vibrance-1 phase 2 publication and extension reporting do not replace long-term blinded comparisons. NCT06843590's September 25 record lists **active, not recruiting**, planned enrollment 126 and November 2026 estimated completion. That status does not establish results or a public readout date.
**Next milestone:** Vibrance 3 November 2026 registry estimate; Brilliance milestones retain their own registry windows. [Vibrance 3 registry](https://clinicaltrials.gov/study/NCT06843590) · [Original status finding](12_sleep.md#vibrance-3-is-now-active-but-no-longer-recruiting) · [Vibrance-1 publication announcement](https://alkermes.gcs-web.com/news-releases/news-release-details/lancet-neurology-publishes-data-alkermes-positive-vibrance-1).
### Other established wake-promoting approaches
The selected sleep–wake explorer includes pitolisant alongside these orexin programs. Approved indication, tested population and endpoint remain product-specific; this inherited baseline is not an exhaustive hypersomnolence formulary. [Pitolisant U.S. prescribing information](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8daa5562-824e-476c-9652-26ceef3d4b0e).
## Rumors and informal signals
#### Anonymous TAK-360 participant describes a tradeoff between wakefulness and nighttime sleep
**Informal statement — unconfirmed; source checked October 16.** In the original r/Narcolepsy thread “A question for anyone doing an orexin agonist clinical trial-(N2 or IH),” **u/statistics_squirrel** says they are in a **Kyra / TAK-360 extension**. They describe stronger daytime wakefulness but insomnia and frequent awakenings at what they consider a higher dose, and say they chose a lower option. They also describe an earlier evening sleep drive and easier morning rising.
The source does not supply a verified dose, diagnosis, investigator assessment or polysomnography. Participation, allocation and symptom causation are unconfirmed. This is one person’s experience, not an incidence rate, dose recommendation, confirmed safety signal or evidence that REM/N3 architecture improved or worsened.
The saved TAK-360 NT2 protocol confirms formal human research, not this individual’s identity or extension enrollment. The rendered comment has relative timestamps; its exact posting date was not independently resolved, so October 16 is the **verification date**. Next: aggregate trial harms, nighttime outcomes and study-specific readouts.
**Sources:** [Source 1](https://www.reddit.com/r/Narcolepsy/comments/1x6wae1/a_question_for_anyone_doing_an_orexin_agonist/); [Source 2](https://clinicaltrials.gov/study/NCT06952699).
## Dated history
### October 3, 2026 — Topic organization
Created this condition-specific entry from existing sleep coverage. Earlier sources, program dates, historical findings and successful research-check timestamps were preserved. See the [organization record](../updates/2026-10-03_sleep_category_organization.md) and [original history](12_sleep.md#dated-history). This is a navigation and baseline projection, not a new medical-news event.