Takeda has reported pivotal results from its Phase III FirstLight and RadiantLight studies of oveporexton (TAK-861), an oral orexin receptor 2 (OX2R)-selective agonist, for the treatment of narcolepsy type 1 (NT1).
The trial results indicated that oveporexton led to significant improvements in daily functioning, cognitive abilities, and sleep quality for individuals with NT1.
Both the FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) studies were global, multi-centre, and placebo-controlled trials.
The FirstLight study involved patients randomised to twice-daily 2mg, 1mg and placebo arms, while RadiantLight used twice-daily 2mg and placebo.
In these studies, oveporexton demonstrated statistically significant improvement at week 12 in daily functioning compared with placebo across the six domains of the Functional Impacts of Narcolepsy Instrument (FINI).
Takeda neuroscience therapeutic area unit and global development head Sarah Sheikh 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 a 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.”
Cognitive improvement was indicated by both objective neuropsychological tests and patient-reported outcomes.
Around 70% of patients across all doses experienced no significant cognitive issues, compared to 15% for placebo.
Exploratory endpoints also revealed better sleep quality, with reductions in hallucinations, sleep paralysis, and disturbed night-time sleep. In addition, rapid eye movement (REM) sleep patterns shifted towards those found in healthy subjects.
Oveporexton remains in regulatory review in China, Japan, and the US, where the Food and Drug Administration accepted its new drug application and granted priority review, with a decision expected in the third quarter.
More than 95% of those who completed the trials have joined an ongoing long-term extension study.
