{ "lastVerified": "2026-08-04", "decisionWindow": { "drug": "oveporexton", "sponsor": "Takeda", "indication": "narcolepsy type 1", "label": "FDA decision window", "window": "Q3 2026", "closes": "2026-09-30", "note": "NDA accepted with Priority Review on 10 Feb 2026. The FDA set a PDUFA target in the third quarter of 2026 without naming a day. As of Takeda's Q1 FY2026 earnings release on 30 Jul 2026, the US application remained under review, with launch preparations underway for the second half of 2026." }, "stages": ["Phase 1", "Phase 2", "Phase 3", "Under review", "Approved"], "programs": [ { "name": "oveporexton", "slug": "oveporexton", "code": "TAK-861", "brand": "ORZEYFUL", "sponsor": "Takeda", "sponsorName": "Takeda Pharmaceutical Company", "mechanism": "Oral selective orexin receptor 2 (OX2R) agonist", "stage": 5, "indications": ["NT1"], "status": "Approved in China on 22 Jul 2026 for adults and adolescents 16 and over — the first oral OX2R-selective agonist approved anywhere. Under Priority Review in the US and under review in Japan.", "evidence": "Phase 3 FirstLight and RadiantLight both met all primary and secondary endpoints.", "flags": ["Breakthrough Therapy", "Priority Review", "Sakigake"], "verified": "2026-08-04", "confidence": "high", "source": "https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-china-narcolepsy/", "detail": [ "Oveporexton is the furthest-advanced drug in this class and the reason the class is being watched at all. It is Takeda's oral, selective orexin receptor 2 agonist, sold under the brand name ORZEYFUL, and on 22 July 2026 it became the first medicine of its kind approved anywhere when Chinese regulators cleared it for adults and adolescents aged 16 and over with narcolepsy type 1.", "Two Phase 3 trials, FirstLight and RadiantLight, both met all primary and secondary endpoints. That is an unusually clean result for a central nervous system programme, where partial hits on secondary endpoints are the norm.", "The applications in the United States and Japan are still pending. The US filing carries Priority Review, which shortens the FDA's review clock, and the programme has previously been granted Breakthrough Therapy designation in the US and Sakigake designation in Japan — both signals that regulators consider the unmet need serious and the early data strong." ], "trials": [], "faq": [ { "q": "Is oveporexton approved?", "a": "Yes, in China. It was approved there on 22 July 2026 for adults and adolescents aged 16 and over with narcolepsy type 1, making it the first oral OX2R-selective agonist approved in any country. It is not yet approved in the United States or Japan, where applications remain under review." }, { "q": "When will the FDA decide on oveporexton?", "a": "The FDA accepted Takeda's New Drug Application with Priority Review on 10 February 2026 and set a PDUFA target date in the third quarter of 2026 without naming a specific day. As of Takeda's Q1 FY2026 earnings release on 30 July 2026 the application was still under review, with launch preparations underway for the second half of 2026." }, { "q": "What is oveporexton's brand name?", "a": "ORZEYFUL. That is the name under which it was approved in China. Brand names can differ by market, so the name used in the United States or Japan may not be the same if those applications are approved." }, { "q": "Did the oveporexton Phase 3 trials succeed?", "a": "Yes. The two pivotal Phase 3 studies, FirstLight and RadiantLight, each met all primary and secondary endpoints." }, { "q": "What else is oveporexton called?", "a": "Its development code is TAK-861 and its brand name in China is ORZEYFUL. All three names refer to the same compound." }, { "q": "How is oveporexton different from TAK-994?", "a": "TAK-994 was Takeda's earlier oral orexin agonist. It was stopped during Phase 2 after liver safety signals emerged. Oveporexton is the successor compound that Takeda carried forward instead." } ] }, { "name": "alixorexton", "slug": "alixorexton", "code": "ALKS 2680", "sponsor": "Alkermes", "sponsorName": "Alkermes plc", "mechanism": "Oral orexin receptor 2 (OX2R) agonist", "stage": 3, "indications": ["NT1", "NT2", "IH"], "status": "Phase 3 Brilliance program opened 1 Apr 2026: Study 302 and Study 304 in NT1, Study 303 in NT2. Vibrance-3 continues in idiopathic hypersomnia at Phase 2.", "evidence": "First oral OX2R agonist to show efficacy in a large Phase 2 study in NT2, where patients are not orexin-deficient.", "flags": ["Breakthrough Therapy", "Enrolling"], "verified": "2026-08-04", "confidence": "high", "source": "https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-initiation-phase-3-brilliance-studies", "detail": [ "Alixorexton is Alkermes' oral OX2R agonist and the second programme in the class to reach Phase 3. The Brilliance programme opened on 1 April 2026 and runs three registrational studies: Study 302 and Study 304 in narcolepsy type 1, and Study 303 in narcolepsy type 2.", "The result that made this programme interesting is in narcolepsy type 2. Patients with NT2 are not orexin-deficient in the way NT1 patients are, so there was a live question about whether adding orexin signalling would help them at all. Alixorexton was the first oral OX2R agonist to show efficacy in a large Phase 2 study in that population.", "A separate study, Vibrance-3, continues at Phase 2 in idiopathic hypersomnia. Alkermes holds Breakthrough Therapy designation for the programme." ], "trials": [], "faq": [ { "q": "What phase is alixorexton in?", "a": "Phase 3 for narcolepsy. The Brilliance programme opened on 1 April 2026 with Study 302 and Study 304 in narcolepsy type 1 and Study 303 in narcolepsy type 2. Its idiopathic hypersomnia study, Vibrance-3, is still at Phase 2." }, { "q": "Does alixorexton work in narcolepsy type 2?", "a": "It was the first oral OX2R agonist to show efficacy in a large Phase 2 study in narcolepsy type 2, a population that is not orexin-deficient. Phase 3 Study 303 is now testing that result in a registrational setting." }, { "q": "Is alixorexton recruiting patients?", "a": "Yes. The Phase 3 Brilliance studies opened on 1 April 2026 and the programme is flagged as enrolling. Recruiting sites and eligibility criteria are listed on ClinicalTrials.gov." }, { "q": "What is ALKS 2680?", "a": "ALKS 2680 is the development code for alixorexton. The two names refer to the same Alkermes compound." } ] }, { "name": "cleminorexton", "slug": "cleminorexton", "code": "ORX750", "sponsor": "Centessa Pharmaceuticals — a wholly owned subsidiary of Eli Lilly since 24 Jun 2026", "sponsorName": "Centessa Pharmaceuticals", "mechanism": "Oral orexin receptor 2 (OX2R) agonist", "stage": 3, "indications": ["NT1", "NT2", "IH"], "status": "A registrational Phase 2/3 study (NCT07598708) opened 29 May 2026: 222 participants with NT1 or NT2, randomized against placebo. The earlier Phase 2 program continues as a long-term extension (NCT07096674) covering NT1, NT2 and IH. Eli Lilly completed its acquisition of Centessa on 24 Jun 2026, making it a wholly owned subsidiary.", "evidence": "Phase 2a data on 55 participants was the first showing of an oral OX2R agonist working across NT1, NT2 and IH.", "flags": ["Enrolling"], "verified": "2026-08-04", "confidence": "high", "source": "https://clinicaltrials.gov/study/NCT07598708", "detail": [ "Cleminorexton is the orexin programme that changed hands. Eli Lilly completed its acquisition of Centessa Pharmaceuticals on 24 June 2026, making the company a wholly owned subsidiary and putting this compound inside one of the largest pharmaceutical organisations in the world.", "A registrational Phase 2/3 study opened on 29 May 2026 and plans to randomise 222 participants with narcolepsy type 1 or type 2 against placebo. The earlier Phase 2 programme continues as a long-term extension covering all three conditions the drug is aimed at: NT1, NT2 and idiopathic hypersomnia.", "The Phase 2a data behind it covered 55 participants and was the first demonstration of an oral OX2R agonist working across NT1, NT2 and IH together — a broader signal than any single-indication result." ], "trials": [ { "nct": "NCT07598708", "what": "Registrational study. 222 participants with NT1 or NT2, randomised against placebo. Opened 29 May 2026.", "phase": "Phase 2/3" }, { "nct": "NCT07096674", "what": "Long-term extension of the earlier Phase 2 programme, covering NT1, NT2 and idiopathic hypersomnia.", "phase": "Phase 2" } ], "faq": [ { "q": "Who owns cleminorexton?", "a": "Eli Lilly. It was developed by Centessa Pharmaceuticals, which Eli Lilly acquired outright on 24 June 2026. Centessa now operates as a wholly owned Lilly subsidiary." }, { "q": "What conditions is cleminorexton being tested in?", "a": "Narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia. The registrational Phase 2/3 study covers NT1 and NT2; the long-term extension covers all three." }, { "q": "What is ORX750?", "a": "ORX750 is the development code for cleminorexton, the Centessa compound now owned by Eli Lilly." }, { "q": "How many people are in the cleminorexton registrational trial?", "a": "222 participants with narcolepsy type 1 or type 2, randomised against placebo. The study, NCT07598708, opened on 29 May 2026." } ] }, { "name": "TAK-360", "slug": "tak-360", "code": "TAK-360", "sponsor": "Takeda", "sponsorName": "Takeda Pharmaceutical Company", "mechanism": "Oral orexin receptor agonist", "stage": 2, "indications": ["NT1", "NT2", "IH"], "status": "Three parallel Phase 2 studies are recruiting: NT1 (NCT07633301), NT2 (NCT06952699) and idiopathic hypersomnia (NCT06812078). A pooled long-term extension safety study across all three conditions (NCT07646678) carries a Phase 2/3 label but is not a pivotal efficacy trial.", "flags": ["Enrolling"], "verified": "2026-08-04", "confidence": "high", "source": "https://clinicaltrials.gov/study/NCT07646678", "detail": [ "TAK-360 is Takeda's second orexin programme, running behind oveporexton. Where oveporexton is aimed squarely at narcolepsy type 1, TAK-360 is being tested across all three of the sleep disorders this class is chasing, in three parallel Phase 2 studies that are recruiting now.", "One point is worth flagging because it is easy to misread. The pooled long-term extension study NCT07646678 carries a Phase 2/3 label on the registry. That label reflects the mix of participants rolling in from earlier studies, not a pivotal efficacy trial. TAK-360 is a Phase 2 programme." ], "trials": [ { "nct": "NCT07633301", "what": "Narcolepsy type 1. Recruiting.", "phase": "Phase 2" }, { "nct": "NCT06952699", "what": "Narcolepsy type 2. Recruiting.", "phase": "Phase 2" }, { "nct": "NCT06812078", "what": "Idiopathic hypersomnia. Recruiting.", "phase": "Phase 2" }, { "nct": "NCT07646678", "what": "Pooled long-term extension safety study across all three conditions. The registry label is Phase 2/3, but this is not a pivotal efficacy trial.", "phase": "Phase 2/3 (label)" } ], "faq": [ { "q": "Is TAK-360 in Phase 3?", "a": "No. TAK-360 is a Phase 2 programme. Its pooled long-term extension safety study, NCT07646678, carries a Phase 2/3 label on ClinicalTrials.gov, but that is an extension study and not a pivotal efficacy trial." }, { "q": "What conditions is TAK-360 being tested in?", "a": "Three, in parallel Phase 2 studies that are recruiting: narcolepsy type 1 (NCT07633301), narcolepsy type 2 (NCT06952699) and idiopathic hypersomnia (NCT06812078)." }, { "q": "How is TAK-360 different from oveporexton?", "a": "Both are Takeda orexin programmes, but oveporexton is approved in China and under review in the US and Japan for narcolepsy type 1, while TAK-360 is still in Phase 2 and is being tested across NT1, NT2 and idiopathic hypersomnia." } ] }, { "name": "E2086", "slug": "e2086", "code": "E2086", "sponsor": "Eisai", "sponsorName": "Eisai Co., Ltd.", "mechanism": "Oral orexin receptor agonist", "stage": 2, "indications": ["NT1"], "status": "Advanced to Phase 2 (NCT07493265, recruiting), evaluating efficacy and safety in adults with narcolepsy, after completed Phase 1 studies including a placebo- and active-comparator-controlled study in NT1.", "flags": ["Enrolling"], "verified": "2026-08-04", "confidence": "high", "source": "https://clinicaltrials.gov/study/NCT07493265", "detail": [ "E2086 is Eisai's entry in the orexin agonist class and the least-covered of the mid-stage programmes. It advanced to Phase 2 with study NCT07493265, now recruiting, which evaluates efficacy and safety in adults with narcolepsy.", "It got there off a Phase 1 package that included a placebo- and active-comparator-controlled study in narcolepsy type 1. Running an active comparator that early is a stronger design than the placebo-only studies typical at Phase 1, because it puts the compound against an existing treatment rather than against nothing." ], "trials": [ { "nct": "NCT07493265", "what": "Efficacy and safety in adults with narcolepsy. Recruiting.", "phase": "Phase 2" } ], "faq": [ { "q": "What phase is E2086 in?", "a": "Phase 2. Study NCT07493265 is recruiting and evaluates efficacy and safety in adults with narcolepsy. It followed completed Phase 1 studies, including a placebo- and active-comparator-controlled study in narcolepsy type 1." }, { "q": "Who makes E2086?", "a": "Eisai, the Japanese pharmaceutical company." } ] }, { "name": "ORX142", "slug": "orx142", "code": "ORX142", "sponsor": "Centessa Pharmaceuticals — a wholly owned subsidiary of Eli Lilly since 24 Jun 2026", "sponsorName": "Centessa Pharmaceuticals", "mechanism": "Orexin receptor agonist", "stage": 1, "indications": ["Neurological", "Neurodegenerative"], "status": "Phase 1 study (NCT07082829) recruiting healthy adults and older adults, including a sleep-deprivation proof-of-concept arm. Centessa describes ORX142 as targeting select neurological and neurodegenerative disorders.", "flags": ["Enrolling"], "verified": "2026-08-04", "confidence": "high", "source": "https://clinicaltrials.gov/study/NCT07082829", "detail": [ "ORX142 is where this class starts to point somewhere other than narcolepsy. Centessa, now owned by Eli Lilly, describes it as targeting select neurological and neurodegenerative disorders rather than sleep disorders specifically.", "The Phase 1 study is recruiting healthy adults and older adults and includes a sleep-deprivation proof-of-concept arm. Enrolling older adults at Phase 1, rather than the usual young healthy volunteers, is consistent with a compound intended for conditions of ageing." ], "trials": [ { "nct": "NCT07082829", "what": "Healthy adults and older adults, including a sleep-deprivation proof-of-concept arm. Recruiting.", "phase": "Phase 1" } ], "faq": [ { "q": "What is ORX142 for?", "a": "Centessa describes it as targeting select neurological and neurodegenerative disorders, not narcolepsy specifically. Its Phase 1 study includes a sleep-deprivation proof-of-concept arm." }, { "q": "What phase is ORX142 in?", "a": "Phase 1. Study NCT07082829 is recruiting healthy adults and older adults." } ] }, { "name": "ORX489", "slug": "orx489", "code": "ORX489", "sponsor": "Centessa Pharmaceuticals — a wholly owned subsidiary of Eli Lilly since 24 Jun 2026", "sponsorName": "Centessa Pharmaceuticals", "mechanism": "Orexin receptor 2 (OX2R) agonist", "stage": 1, "indications": ["Neuropsychiatric"], "status": "Now in a Phase 1 study (NCT07413666) in healthy adults, past the IND-enabling stage it was in previously. Centessa's most potent OX2R agonist to date, being developed for neuropsychiatric disorders.", "flags": ["Enrolling"], "verified": "2026-08-04", "confidence": "high", "source": "https://clinicaltrials.gov/study/NCT07413666", "detail": [ "ORX489 is Centessa's most potent OX2R agonist to date and is being developed for neuropsychiatric disorders — again, a target outside the sleep-disorder core of this class.", "It has moved past the IND-enabling stage it previously sat at and is now in a Phase 1 study in healthy adults." ], "trials": [ { "nct": "NCT07413666", "what": "Healthy adults. Recruiting.", "phase": "Phase 1" } ], "faq": [ { "q": "What is ORX489 being developed for?", "a": "Neuropsychiatric disorders. Centessa describes it as its most potent OX2R agonist to date." }, { "q": "What phase is ORX489 in?", "a": "Phase 1. Study NCT07413666 is running in healthy adults, having moved past the IND-enabling stage the compound previously sat at." } ] }, { "name": "ALKS 4510", "slug": "alks-4510", "code": "ALKS 4510", "sponsor": "Alkermes", "sponsorName": "Alkermes plc", "mechanism": "Orexin receptor agonist", "stage": 1, "indications": ["Fatigue in MS", "Fatigue in Parkinson's"], "status": "Phase 1, in development for fatigue associated with multiple sclerosis and Parkinson's disease, per Alkermes' own pipeline page. Not yet listed on ClinicalTrials.gov under this compound name.", "flags": [], "verified": "2026-08-04", "confidence": "high", "source": "https://www.alkermes.com/research-and-development/pipeline", "detail": [ "ALKS 4510 aims the orexin mechanism at fatigue associated with multiple sclerosis and Parkinson's disease — two conditions where debilitating fatigue is common and poorly served by existing treatments.", "It sits at Phase 1 on Alkermes' own pipeline page and is not yet listed on ClinicalTrials.gov under this compound name, so there is no public trial record to read yet." ], "trials": [], "faq": [ { "q": "What is ALKS 4510 for?", "a": "Fatigue associated with multiple sclerosis and Parkinson's disease, according to Alkermes' pipeline page." }, { "q": "Can I find the ALKS 4510 trial on ClinicalTrials.gov?", "a": "Not yet. As of the last check on 4 August 2026 it was not listed on ClinicalTrials.gov under this compound name. The only public source is Alkermes' own pipeline page." } ] }, { "name": "ALKS 7290", "slug": "alks-7290", "code": "ALKS 7290", "sponsor": "Alkermes", "sponsorName": "Alkermes plc", "mechanism": "Orexin receptor agonist", "stage": 1, "indications": ["ADHD"], "status": "Phase 1, in development for attention-deficit hyperactivity disorder, per Alkermes' own pipeline page. Not yet listed on ClinicalTrials.gov under this compound name.", "flags": [], "verified": "2026-08-04", "confidence": "high", "source": "https://www.alkermes.com/research-and-development/pipeline", "detail": [ "ALKS 7290 points the orexin mechanism at attention-deficit hyperactivity disorder. It is the furthest any programme in this class strays from sleep medicine, and the clearest sign that sponsors see orexin signalling as a lever on wakefulness and attention generally rather than on narcolepsy alone.", "It sits at Phase 1 on Alkermes' own pipeline page and is not yet listed on ClinicalTrials.gov under this compound name." ], "trials": [], "faq": [ { "q": "What is ALKS 7290 for?", "a": "Attention-deficit hyperactivity disorder, according to Alkermes' pipeline page." }, { "q": "What phase is ALKS 7290 in?", "a": "Phase 1. It is not yet listed on ClinicalTrials.gov under this compound name, so Alkermes' pipeline page is the only public source." } ] } ], "halted": [ { "name": "TAK-994", "slug": "tak-994", "sponsor": "Takeda", "status": "Stopped in Phase 2 after liver safety signals emerged. Oveporexton is the successor compound.", "verified": "2026-08-04", "source": "https://www.nejm.org/doi/full/10.1056/NEJMoa2301940" }, { "name": "danavorexton", "slug": "danavorexton", "sponsor": "Takeda", "status": "TAK-925, an intravenous OX2R agonist used to establish the mechanism in humans. Superseded by oral compounds.", "verified": "2026-08-04", "source": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515106/" }, { "name": "JZP441", "slug": "jzp441", "sponsor": "Jazz Pharmaceuticals", "status": "Oral OX2R agonist licensed from Sumitomo Pharma (as DSP-0187). The Phase 1b efficacy study in narcolepsy type 1 (NCT06961266) was terminated in early 2026 for business reasons, not a safety signal. The compound no longer appears on Jazz's pipeline page.", "verified": "2026-08-04", "source": "https://clinicaltrials.gov/study/NCT06961266" } ] }