New Oral Medicine for Narcolepsy Type 1 in Adults

Narcolepsy type 1 is the form with cataplexy, driven by loss of orexin (hypocretin) signaling. Existing medicines treat pieces of it — stimulants for sleepiness, other drugs for cataplexy. Orzeyful (oveporexton, TAK-861) is an oral orexin receptor 2 (OX2R) agonist. It is the first labelled medicine that acts on that missing signal.

The FDA labelled it on 5 August 2026 for adults with narcolepsy type 1. The same FDA announcement says it has been recommended for scheduling under the Controlled Substances Act and will be lawful to market following the DEA’s scheduling decision. The US prescribing information still reads “controlled substance schedule pending.” US pharmacies are not open for a routine fill today.

Japan’s PMDA published the August 2026 new-drug list with オーゼイフル錠 (oveporexton) approved 24 August 2026 for narcolepsy type 1. China’s NMPA approval is a Takeda China company announcement dated 22 July 2026 for people aged 16 years and older and adults — that age line is not the US line, and the nmpa.gov.cn decision page was not retrieved here.

Health Canada accepted a new-drug submission in July 2026. As of the SUR list dated 31 July 2026, oveporexton is under review. That is not a no.

Narcolepsy type 2 and idiopathic hypersomnia are not on these labels.

Where this is taking place

FirstLight (TAK-861-3001, NCT06470828) — COMPLETED. Phase 3, 12 weeks, n=168 actual (placebo 41 / 1 mg BID 61 / 2 mg BID 66). Ages 16 to 70 on CT.gov. Sponsor: Takeda. Countries with listed sites include the United States, Canada (Ottawa, Toronto, Montreal — historical, not enrolment), France, Germany, Italy, Japan, the Netherlands, Norway, Spain, Switzerland, and the United Kingdom. Results posted 31 Aug 2026. Not an enrolment path.

RadiantLight (TAK-861-3002, NCT06505031) — COMPLETED. Phase 3, 12 weeks, n=105 actual (placebo 35 / 2 mg BID 70). Ages 18 to 70 on CT.gov. Sites include Australia, Austria, Belgium, China, Finland, France, Italy, Poland, South Korea, Spain, and Sweden. No US or Canadian sites on this record. Results posted 16 Jul 2026. Not an enrolment path.

FDA news: two 12-week studies, 273 adults in total. That is 168 + 105.

LTE (TAK-861-2003, NCT05816382) — RECRUITING. Open-label extension. Door: people with NT1 who already finished a controlled TAK-861 parent trial, and for whom the investigator has no clinical objection. NT2 participants from the phase 2 parent were discontinued after that study missed its prespecified bar. Estimated n=500; primary completion estimated 28 Feb 2028. CT.gov locations: United States, Australia, Finland, France, Germany, Italy, Japan, the Netherlands, Norway, Spain, Sweden, Switzerland. Canada is not on that location list. This is not a first-script trial.

NCT07363720 — Phase 3 randomized-withdrawal, ACTIVE_NOT_RECRUITING. Not an enrolment path.

NCT05687903 (phase 2b NT1) and NCT05687916 (phase 2 NT2) — COMPLETED. NT2 is not labelled.

Commercial supply: United States — not lawful to market until DEA publishes interim final scheduling and Takeda files the labeling supplement. Japan: PMDA-listed; first dispense unknown. China: company NMPA; nmpa.gov.cn not retrieved; launch unknown. Canada: not marketed.

Approval matrix (narcolepsy type 1)

China’s 16+ company line is not the US or Japan adult label. Use the label of the country that will prescribe.

Access by country

• United States: Sleep / neurology clinic. FDA labelled 5 Aug 2026 for adults with NT1. US pharmacies cannot lawfully dispense until DEA publishes interim final scheduling in the Federal Register and Takeda supplements the label. orzeyful.com still says pending DEA. Company “November 2026” and “specialty pharmacy” are company, not a fill date and not a USPI mandate. The USPI does not require a REMS. Prior authorization will still apply once it is marketable. No copay dollars here. Adverse reactions (USPI): Takeda 1-877-TAKEDA-7 (1-877-825-3327) or FDA 1-800-FDA-1088. Pregnancy registry (USPI): 1-877-371-0309. Those are AE / pregnancy contacts on the USPI, not a savings card.
• Japan: In-country path after MHLW/PMDA 24 Aug 2026 for NT1. Tablets 0.5 / 1 / 2 mg. Takeda’s Japan overview: usual adult dose 1 mg twice daily (first dose on awakening, second 3–5 hours later); may increase to 2 mg twice daily only if tolerated and effect is not enough. First Japanese dispense and NHI listing unknown. Not a Canadian travel path.
• China: In-country commercial only if NMPA has authorised — Takeda China says yes, 22 Jul 2026, ages 16+ and adults. nmpa.gov.cn was not retrieved. NRDL not found. Not a Canadian travel path.
• United Kingdom: Narcolepsy UK: not available. NICE GID-TA11820 is in progress (committee 9 Feb 2027, guidance expected 14 Apr 2027) — not a yes. MHRA marketing authorisation unknown here. Ask the sleep clinic; do not DIY-import.
• European Union: Centralised MA unknown. A PIP is not a prescription. National reimbursement unknown. Travelling from an unlabelled country for an EU script is a medical/legal plan with both specialists — and there is no retrieved EU MA to travel toward today.
• Canada (zoom): No NOC. SUR under review (accepted Jul 2026; list current 31 Jul 2026). Aligned HTA review is on that SUR row; CDA-AMC file number not retrieved. That is not a no. A specialist can ask Health Canada SAP for a non-marketed drug when conventional therapy has failed, is unsuitable, or is unavailable. Manufacturer must agree to supply. SAP unknown — not available and not refused. FirstLight Canadian sites (Ottawa, Toronto, Montreal) are historical, not enrolment. LTE is completers only and does not list Canada on CT.gov.
• Australia / Switzerland: Authorisation unknown. Specialist + local special-access / trial if those programs apply.

If your regulator has not authorised it: do not import on your own. Travelling to the United States for a commercial script does not work while DEA scheduling is pending. Travelling to Japan or China is an in-country plan with both specialists, not a mail-order workaround — and China still sits on a company announcement until nmpa.gov.cn is in hand.

What the pivotal trials showed

These numbers are from the USPI Table 3 (Studies 1 and 2) unless marked as CT.gov. They are 12-week trials, not a cure.

Study 1 / FirstLight (NCT06470828). Mean age 31 (range 16–65 on the USPI). MWT mean sleep latency, LS mean change: placebo −1.3 min; 1 mg BID +12.5; 2 mg BID +15.9. Difference vs placebo 13.8 (10.2–17.4) and 17.2 (13.7–20.7) minutes. ESS: −1.4 vs −9.4 vs −11.2 (differences −8.0 and −9.8). Weekly cataplexy incidence-rate ratio vs placebo 0.34 (1 mg) and 0.38 (2 mg).

Study 2 / RadiantLight (NCT06505031). Mean age 31 (range 18–62). 2 mg BID only vs placebo. MWT: −1.0 vs +19.1 min (difference 20.1; 16.6–23.6). ESS: −1.6 vs −11.1 (difference −9.5). Cataplexy IRR 0.25 (0.15–0.42).

Pooled USPI warnings (Studies 1 and 2): insomnia 60% / 55% / 1% (2 mg / 1 mg / placebo); urinary frequency 58% / 53% / 5%; urinary urgency 16% / 15% / 1%. Discontinuation for adverse reactions 2.6% vs 1.3%. Asymptomatic CPK >5× ULN 11% vs 5%. LDL >160 mg/dL 32% vs 20%. Day-1 blood-pressure and heart-rate bumps were more common on drug; 24-hour monitoring at week 10 did not show a lasting difference.

Phase 2b (NCT05687903 / NEJM) is background, not the labelled 12-week program.

This is a twice-daily OX2R agonist that, in two 12-week trials, moved wakefulness, sleepiness, and cataplexy. It is not a cure. It is not labelled for narcolepsy type 2.

How it is taken (US label)

USPI recommended dosage, adults:

• 1 mg orally after awakening, then 1 mg three to five hours later, or
• 2 mg then 2 mg on the same schedule.
• Maximum 4 mg per day.
• Swallow whole with water. Do not split, crush, or chew. With or without food. Same time each day. If a dose is missed, skip it; do not double.

Strong CYP3A inhibitors: do not take (contraindicated). Moderate CYP3A inhibitors: reduce to 0.5 mg then 0.5 mg (max 1 mg/day). Avoid strong or moderate CYP3A inducers.

Avoid in Child-Pugh C and in eGFR <15 mL/min on dialysis (not studied). Mild/moderate hepatic or non-dialysis renal impairment: same dose as normal function.

Japan’s company overview starts at 1 mg BID and only then allows 2 mg BID. That is not the US “either 1 mg BID or 2 mg BID” line. Use the label of the country that will prescribe.

Pediatrics: US — not established under 18 (even though FirstLight enrolled from 16). China company line — 16+. Japan company overview — adults. US under-18, China 16+, and Japan adults stay separate labelled lines.

Pregnancy: human data insufficient. USPI pregnancy registry 1-877-371-0309. Lactation: present in rat milk; human milk unknown.

Abuse: USPI says potential for abuse and misuse; human abuse-potential scores greater than placebo and similar to or lower than phentermine 75 mg. Schedule to be determined by DEA.

Research team (Who)

Names below are as they appear on primary sources.

• Takeda — sponsor (FirstLight, RadiantLight, LTE, phase 2). NCT overall official: “Medical Director / Study Director,” unnamed.
• Takeda Pharmaceuticals America, Inc. — FDA applicant / USPI distributor (Cambridge, MA).
• Takeda Canada Inc. — Health Canada SUR applicant.
• 武田薬品工業株式会社 — Japan MAH on the PMDA August 2026 list.
• Takeda US approval press names Emmanuel Mignot, M.D., Ph.D. as “principal U.S. investigator in the ORZEYFUL Phase 3 program.” That is company, not the NCT official.
• Phase 2b NEJM: TAK-861-2001 / NCT05687903 (Dauvilliers et al., DOI 10.1056/NEJMoa2405847).

No Canadian PI is named on CT.gov. FirstLight’s three Canadian cities are historical sites, not a clinic directory.

How to talk to a doctor

Bring the NCT numbers and the regulator that applies:

1. “I have narcolepsy type 1 (with cataplexy). Is oveporexton labelled where we are — US adults, Japan adults, or China 16+ — or are we still on stimulants / oxybate / pitolisant?”
2. If US: “The FDA labelled it on 5 August 2026, but DEA has not published scheduling. Are you preparing a prescription for after that notice, or is that premature?”
3. Strong CYP3A inhibitors (contraindicated), moderate inhibitors (dose reduction), inducers (avoid). Urinary symptoms, insomnia in the first week, unexplained muscle pain or dark urine (CPK).
4. If 16 or 17: “The US label does not establish use under 18. China’s company line is 16+. Do not write me the US adult tablet off a China press release.”
5. If Canada: “The NDS is under review as of 31 July 2026. Is SAP appropriate, or do we wait for the NOC? LTE is completers only and does not list Canada.”
6. If UK: “Narcolepsy UK says it is not available. NICE GID-TA11820 is not a recommendation yet.”
7. If NT2 or idiopathic hypersomnia: “That is not labelled. Do not write oveporexton from a phase 2 miss.”

Canada zoom: under review / SAP unknown

Health Canada is under review. SAP for a non-marketed drug is unknown — not a listing, not a refusal. Canada is not dual Health Canada/FDA Approved on a SUR. US: labelled on paper, not marketable until DEA. Japan: PMDA-listed; launch unknown. China: company NMPA until nmpa.gov.cn. LTE is completers only. Do not mail-order.

Bottom line

Orzeyful (oveporexton) is an oral OX2R agonist labelled for narcolepsy type 1. United States: FDA 5 Aug 2026, adults, DEA gate still down — not a US pharmacy fill today. Japan: PMDA list 24 Aug 2026; first fill unknown. China: Takeda says NMPA 22 Jul 2026 for ages 16+ and adults; nmpa.gov.cn not retrieved. Health Canada: under review, not refused. UK: not available; NICE in 2027, not a yes. NT2 is not labelled. Authorized is not on the shelf, except where a local pharmacy can already legally dispense — and in the US, that is after DEA, not before. Canada is a zoom.

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Primary sources

1. FDA news, 5 Aug 2026 — https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-full-range-narcolepsy-type-1-symptoms
2. FDA Novel Drug Approvals 2026 (Orzeyful / oveporexton, 8/5/2026) — https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026
3. Drugs@FDA NDA 220860 — https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=220860
4. USPI, Revised 8/2026 — https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220860Orig1s000lbl.pdf
5. FDA approval letter, NDA 220860 (21 U.S.C. 355(x) DEA gate) — https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/220860Orig1s000ltr.pdf
6. DailyMed search (0 results, 2026-09-02) — https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=orzeyful
7. Federal Register API (0 documents, 2026-09-02) — https://www.federalregister.gov/api/v1/documents.json?conditions%5Bterm%5D=oveporexton
8. Takeda US approval, 5 Aug 2026 (company; specialty pharmacy / 90-day DEA) — https://www.takeda.com/en-us/newsroom/news-releases/2026/orzeyful-approved-narcolepsy/
9. orzeyful.com (pending DEA; company November 2026) — https://www.orzeyful.com/
10. Health Canada SUR, current 2026-07-31 (Oveporexton, accepted 2026-07, Takeda Canada Inc) — https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-review/new-drug-submissions-under-review.html
11. Takeda China, 22 Jul 2026 (company NMPA; ages 16+) — https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-china-narcolepsy/
12. PMDA 承認品目一覧（新医薬品：2026年8月）— https://www.pmda.go.jp/files/000281577.pdf
13. PMDA 2026年度承認品目一覧 index — https://www.pmda.go.jp/review-services/drug-reviews/review-information/p-drugs/0040.html
14. Takeda Japan, 24 Aug 2026 (company product overview: adult 1 mg BID, may increase to 2 mg BID) — https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-japan-narcolepsy/
15. NICE GID-TA11820 / ID6622 — https://www.nice.org.uk/guidance/indevelopment/gid-ta11820
16. Narcolepsy UK, oveporexton not available — https://www.narcolepsy.org.uk/major-oveporexton-milestones-reached/
17. MHRA PIP MHRA-101278-PIP01-23 — https://cms.mhra.gov.uk/pip/mhra-101278-pip01-23-0
18. EMA medicines under evaluation — https://www.ema.europa.eu/en/medicines/medicines-human-use-under-evaluation
19. FirstLight NCT06470828 — https://clinicaltrials.gov/study/NCT06470828
20. RadiantLight NCT06505031 — https://clinicaltrials.gov/study/NCT06505031
21. LTE NCT05816382 — https://clinicaltrials.gov/study/NCT05816382
22. NCT07363720 (ACTIVE_NOT_RECRUITING) — https://clinicaltrials.gov/study/NCT07363720
23. Phase 2b NCT05687903 / NEJM DOI 10.1056/NEJMoa2405847 — https://www.nejm.org/doi/full/10.1056/NEJMoa2405847