Takeda  unveiled promising topline results from a comprehensive Phase 2b trial evaluating TAK-861, an oral orexin receptor 2 (OX2R) agonist, in patients diagnosed with narcolepsy type 1 (NT1). Narcolepsy, characterized by central hypersomnolence, poses significant challenges despite existing therapeutic options. NT1, marked by a deficiency in orexin neurons, constitutes a substantial unmet need within the narcolepsy landscape.

In the NT1 trial, designated TAK-861-2001, 112 patients participated in a randomized, double-blind, placebo-controlled study. The trial showcased statistically significant and clinically meaningful improvements in objective and subjective measures of wakefulness compared to placebo at week 8, including the primary endpoint Maintenance of Wakefulness Test (MWT) (p < 0.001). Additional key secondary endpoints, such as the Epworth Sleepiness Scale (ESS) and Weekly Cataplexy Rate (WCR), also exhibited statistically significant and clinically relevant enhancements, reinforcing the efficacy of TAK-861 in addressing the core symptoms of NT1.

Sarah Sheikh M.Sc., B.M., B.Ch, MRCP, Head of the Neuroscience Therapeutic Area Unit and Global Development at Takeda, expressed enthusiasm regarding the trial results. "We are thrilled to announce these clear and compelling results from the TAK-861 trial in narcolepsy type 1 that allows us to rapidly initiate Phase 3 trials this year as we work to deliver a medicine to patients that could address the underlying pathophysiology of the disease," said Sheikh. "Takeda thanks the patients, caregivers, and investigators who participated in our orexin agonist trials. We will continue to apply our deep and growing understanding of orexin biology as we work to develop and deliver transformative treatments to people across a range of indications who could benefit from this mechanism."

Crucially, TAK-861 demonstrated a favorable safety profile, with no treatment-related serious adverse events reported in either the Phase 2b trials or the ongoing long-term extension study. Furthermore, incidences of hepatotoxicity or visual disturbances were notably absent, affirming the tolerability of TAK-861.

Building upon these encouraging findings, Takeda intends to expedite the initiation of global Phase 3 trials of TAK-861 in NT1 within the first half of fiscal year 2024. While plans for advancing TAK-861 in narcolepsy type 2 (NT2) are not currently underway, Takeda remains committed to exploring the potential of orexin agonists across various patient populations and indications where orexin biology is implicated.

Results from both the NT1 and NT2 trials are slated for presentation at an upcoming scientific congress, underscoring Takeda's commitment to transparency and collaboration within the scientific community