The investigational orexin receptor 2 agonist showed statistically significant and clinically meaningful improvements across primary and secondary endpoints in patients with narcolepsy type 1.


Summary: TAK-861, an investigational oral orexin receptor 2 (OX2R) agonist developed by Takeda, demonstrated significant and sustained improvements in the treatment of narcolepsy type 1 in a phase 2b clinical trial. The study involved 112 patients and showed positive results across primary and secondary endpoints, including increased sleep latency and reduced sleepiness and cataplexy frequency. The drug was well-tolerated with no serious treatment-related adverse events. Takeda plans to initiate global phase 3 trials in 2024 based on these results.

Key Takeaways:

  • TAK-861 showed statistically significant and clinically meaningful improvements in sleep latency, sleepiness, and cataplexy frequency in patients with narcolepsy type 1, sustained over an eight-week period.
  • The phase 2b trial indicated that TAK-861 was generally safe and well-tolerated, with no serious treatment-related adverse events reported. Common mild to moderate side effects included insomnia, urinary urgency and frequency, and salivary hypersecretion.
  • Based on the phase 2b results, Takeda plans to launch global phase 3 trials of TAK-861 in 2024, and the drug has received Breakthrough Therapy designation from the FDA for the treatment of excessive daytime sleepiness in narcolepsy type 1.

TAK-861, an investigational oral orexin receptor 2 (OX2R) agonist in development by Takeda, demonstrated statistically significant and clinically meaningful improvements in the treatment of narcolepsy type 1 in a phase 2b clinical trial.

The improvements were seen across primary and secondary endpoints, with efficacy sustained over eight weeks of treatment. The randomized, double-blind, placebo-controlled, multiple-dose trial, TAK-861-2001, involved 112 patients with narcolepsy type 1. 

Takeda is presenting results from the trial at SLEEP 2024. 

Tackling Narcolepsy Type 1

Narcolepsy type 1 is caused by a significant loss of orexin neurons, resulting in low levels of orexin neuropeptides in the brain and cerebrospinal fluid. No currently approved treatments target the underlying pathophysiology of narcolepsy type 1, according to a release from Takeda. 

TAK-861 is designed to address the orexin deficiency by selectively stimulating the orexin receptor 2.

The presentation highlights results from the phase 2b trial including:

  • The primary endpoint demonstrated statistically significant and clinically meaningful increased sleep latency on the Maintenance of Wakefulness Test versus placebo across all doses. Improvements were sustained over eight weeks.
  • Consistent results were achieved in the key secondary endpoints including the Epworth Sleepiness Scale and Weekly Cataplexy Rate, demonstrating significantly improved subjective measures of sleepiness and cataplexy frequency versus placebo that were also sustained over eight weeks.
  • The majority of narcolepsy type 1 patients in the trial were found to be within normative ranges for Maintenance of Wakefulness Test and Epworth Sleepiness Scale by the end of the eight-week treatment period as a result of these sustained improvements.
  • The majority of the participants who completed the trial enrolled in the long-term extension study with some patients reaching one year of treatment.
  • The trial also included additional exploratory endpoints that showed meaningful improvements in narcolepsy symptoms and functioning according to most participants. These data will also be presented in poster presentations at SLEEP and at future scientific congresses.
  • The dataset showed that TAK-861 was generally safe and well tolerated during the study, with no treatment-related serious treatment-emergent adverse events (TEAEs) or discontinuations due to TEAEs.
  • No cases of hepatotoxicity or visual disturbances were reported in the Phase 2b trial or in the ongoing long-term extension study. The most common TEAEs were insomnia, urinary urgency and frequency, and salivary hypersecretion. Most TEAEs were mild to moderate in severity, and most started within one to two days of treatment and were transient.

Heading Toward Phase 3 Trials

Based on these results, and in consultation with global health authorities, Takeda plans to initiate global phase 3 trials of TAK-861 in narcolepsy type 1 in the first half of its fiscal year 2024. 

The phase 2b data also supported the recent Breakthrough Therapy designation for TAK-861 for the treatment of excessive daytime sleepiness in narcolepsy type 1 from the US Food and Drug Administration. Breakthrough Therapy designation is a process designed to expedite the development and review of a drug that is intended to treat a serious or life-threatening condition, for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on at least one clinically significant endpoint.

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