Takeda Pharmaceutical Company presented new clinical trial data at Sleep Europe 2024, highlighting the potential of TAK-861, an investigational oral orexin receptor 2 (OX2R) selective-agonist, in treating narcolepsy type 1 (NT1). The data, derived from Phase 2b trials (TAK-861-2001, TAK-861-2002) and a long-term extension (LTE) study (TAK-861-2003), demonstrate the drug's impact on daily functioning, cognition, and sleep quality in NT1 patients.
Impact on Daily Functioning and Cognition
One of the key presentations focused on the effect of TAK-861 on cognitive impairment in NT1 patients (Abstract No: 781). Narcolepsy is characterized by excessive daytime sleepiness and cataplexy, but also by significant cognitive deficits that impact daily life. The data presented at Sleep Europe 2024 suggests that TAK-861 could improve these cognitive impairments, offering a more comprehensive treatment approach.
Improvements in Nocturnal Sleep Quality
Additional poster presentations explored the impact of TAK-861 on other exploratory endpoints, including the quality of nocturnal sleep and sustained attention. These findings suggest that TAK-861 not only addresses daytime symptoms but also improves the restorative aspects of sleep, which are often disrupted in narcolepsy patients.
Long-Term Efficacy and Safety
An interim analysis of safety and efficacy from the ongoing LTE study (Poster No: P1291) was also presented. This analysis provided insights into the long-term effects of TAK-861, with some patients having received treatment for up to one year. The data supports the sustained efficacy and safety of TAK-861, reinforcing its potential as a long-term treatment option for NT1.
Phase 3 Trial Underway
Based on the promising Phase 2b results, Takeda has initiated the FirstLight Study, a global Phase 3 trial evaluating the efficacy and safety of TAK-861 in adults with NT1 (NCT06470828). This trial is currently enrolling patients and represents a significant step forward in the development of TAK-861 as a potential new treatment for narcolepsy.
Addressing Orexin Deficiency in NT1
TAK-861 is designed to address the underlying pathophysiology of NT1, which is characterized by a deficiency in orexin, a key regulator of the sleep-wake cycle. By selectively stimulating the orexin receptor 2 (OX2R), TAK-861 aims to restore normal sleep-wake patterns and alleviate the symptoms of narcolepsy. If approved, TAK-861 has the potential to be the first treatment to directly target the root cause of NT1.
Takeda's Broader Orexin Agonist Program
Takeda is also developing other orexin agonists, including TAK-360, an oral OX2R agonist being investigated for narcolepsy type 2 (NT2) and idiopathic hypersomnia. TAK-360 recently initiated a Phase 1 trial and received Fast Track designation from the FDA. These efforts underscore Takeda's commitment to advancing the field of orexin therapeutics and addressing the unmet needs of patients with various sleep-wake disorders.
Elena Koundourakis, head of orexin franchise development & neuroscience programs and portfolio strategy at Takeda, stated, "As leaders in orexin science, we continue to develop one of the most extensive clinical datasets of orexin agonists... The data we are presenting at Sleep Europe add to the body of orexin agonist data we are building to improve our understanding of orexin biology and the potential of our investigative study drug TAK-861 towards establishing a new standard of care for the NT1 community."
