Takeda's TAK-861 Phase 2b Data Shows Significant Impact in Narcolepsy Type 1 at SLEEP 2024

Takeda has announced promising results from its Phase 2b trial of TAK-861, an investigational oral orexin receptor 2 (OX2R) agonist, for narcolepsy type 1 (NT1) at SLEEP 2024. The trial, named TAK-861-2001 (NCT05687903), included 112 NT1 patients and aimed to assess the efficacy and safety of TAK-861. The study was randomized, double-blind, and placebo-controlled.

NT1 is a severe neurological condition characterized by a significant loss of orexin neurons, leading to low levels of orexin neuropeptides, which are crucial for regulating wakefulness. Symptoms of NT1 include excessive daytime sleepiness (EDS), cataplexy, disrupted sleep, hallucinations, and sleep paralysis, significantly impairing quality of life. Existing treatments for NT1 do not target its underlying pathophysiology.

The trial results showcased statistically significant and clinically meaningful improvements across both primary and secondary endpoints. Primary outcomes were measured using the Maintenance of Wakefulness Test (MWT), where TAK-861 showed increased sleep latency compared to placebo across all doses, with improvements sustained over the 8-week treatment duration. Secondary endpoints included the Epworth Sleepiness Scale (ESS) and Weekly Cataplexy Rate (WCR), which also showed significant improvements in sleepiness and reduction in cataplexy frequency compared to placebo, maintained throughout the study period.

Most participants reached normative ranges for MWT and ESS by the end of the trial. A majority of the patients who completed the trial enrolled in a long-term extension (LTE) study, with some continuing treatment for up to a year. Exploratory endpoints also indicated meaningful improvements in symptoms and overall functioning, which will be detailed in future presentations.

Safety data from the study indicated that TAK-861 was generally well tolerated. No serious treatment-emergent adverse events (TEAEs) related to the drug were reported, and no discontinuations occurred due to TEAEs. Specific adverse events included insomnia, urinary urgency, frequency, and salivary hypersecretion, most of which were mild to moderate and transient. Notably, there were no reports of hepatotoxicity or visual disturbances.

Sarah Sheikh, M.D., M.Sc., B.M., B.Ch., MRCP, Head of the Neuroscience Therapeutic Area Unit and Global Development at Takeda, emphasized the potential of TAK-861 to become a new standard of care for NT1, highlighting the company's commitment to exploring the full potential of orexin biology. Takeda plans to initiate global Phase 3 trials for TAK-861 in the first half of fiscal year 2024, following recent consultations with global health authorities.

The Phase 2b trial results also contributed to the U.S. FDA's recent Breakthrough Therapy designation for TAK-861, aimed at expediting the development and review process for treatments showing substantial improvement over existing therapies for serious conditions.

Takeda's orexin franchise extends beyond TAK-861, including TAK-360 and danavorexton (TAK-925). TAK-360, an oral OX2R agonist, is in a Phase 1 trial for narcolepsy type 2 and idiopathic hypersomnia, having received Fast Track designation from the FDA. Danavorexton, an intravenously administered OX2R agonist, is being investigated in a Phase 2 trial for patients with moderate to severe obstructive sleep apnea undergoing general anesthesia.

Takeda, a biopharmaceutical company headquartered in Japan, focuses on creating transformative treatments in areas like gastrointestinal disorders, rare diseases, oncology, neuroscience, and vaccines. Their dedication to improving patient experiences and advancing treatment options drives their research and development efforts.

In summary, TAK-861's Phase 2b trial results highlight its potential to significantly improve NT1 symptoms, with a positive safety profile. As Takeda prepares for Phase 3 trials, the future looks promising for NT1 patients seeking more effective treatment options.