Takeda disclosed pivotal Phase III results showing that oveporexton (TAK-861), an oral OX2R-selective agonist, improved daily functioning, cognition and sleep quality in people with narcolepsy type 1. Both global, placebo-controlled FirstLight and RadiantLight trials met their key endpoints, with significant week-12 gains across all six FINI domains. About 70% of treated patients had no meaningful cognitive impairment versus ~15% on placebo, and REM sleep measures shifted toward healthy norms. Oveporexton is under review in China, Japan and the U.S., where the FDA has granted priority review with a decision expected in Q3.
Takeda: Oveporexton Delivers Pivotal Phase III Benefits in Narcolepsy Type 1
The FirstLight study involved patients randomised to twice-daily 2mg
Takeda has reported pivotal Phase III results from its global, multicentre, placebo-controlled FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) trials evaluating oveporexton (TAK-861), an oral orexin receptor 2 (OX2R)-selective agonist, for people with narcolepsy type 1 (NT1).
Study Design and Dosing
The two randomized trials compared twice-daily doses of oveporexton against placebo:
- FirstLight (TAK-861-3001): randomized to 2 mg twice daily, 1 mg twice daily, or placebo.
- RadiantLight (TAK-861-3002): randomized to 2 mg twice daily or placebo.
Key Efficacy Findings
At week 12, oveporexton demonstrated statistically significant improvement versus placebo in daily functioning across all six domains of the Functional Impacts of Narcolepsy Instrument (FINI). Cognitive benefits were supported by objective neuropsychological testing and patient-reported outcomes.
Sarah Sheikh, Head of Takeda’s Neuroscience Therapeutic Area Unit and Global Development, said: "Narcolepsy type 1 is not defined by a single symptom, which is why we designed a comprehensive Phase III programme to evaluate the effect of oveporexton on the broad disease impact. We are grateful to the patients, caregivers and healthcare providers who have been part of this journey. With oveporexton under review by multiple regulatory agencies, we are on the cusp of bringing the first and only orexin agonist to the narcolepsy type 1 community, with the potential to redefine the standard of care if approved."
Approximately 70% of patients across active doses experienced no clinically meaningful cognitive impairment, compared with roughly 15% in placebo groups. Exploratory endpoints also indicated improved nocturnal sleep and fewer parasomnias, including reductions in hallucinations, episodes of sleep paralysis, and disturbed night-time sleep. Polysomnography showed REM sleep measures moving closer to patterns observed in healthy subjects.
Regulatory Status and Next Steps
Oveporexton is under regulatory review in multiple jurisdictions, including China, Japan and the United States. The U.S. Food and Drug Administration has accepted the new drug application and granted priority review, with a regulatory decision expected in the third quarter. More than 95% of participants who completed the controlled trials have enrolled in an ongoing long-term extension study to gather additional safety and durability data.
Source and Note: These results were reported by Takeda and originally published by Hospital Management (a GlobalData brand). This summary is for informational purposes only and is not medical advice. Clinical benefit and approval remain subject to regulatory review and final agency decisions.
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