Takeda announced positive topline results from a randomized, double-blind, placebo-controlled, multiple-dose phase 2b trial evaluating TAK-861, an oral orexin receptor 2 (OX2R) agonist, in patients with narcolepsy type 1.

Two separate phase 2b studies were conducted in narcolepsy type 1 (NCT05687903) and narcolepsy type two (NCT05687916). Narcolepsy type 1 is caused by a significant loss of orexin neurons with a resulting lack of orexin, while in narcolepsy type 2, orexin levels are generally normal. Stimulating the orexin receptor 2 in narcolepsy type 1 patients targets the underlying pathophysiology of the disease to restore orexin signaling. 

The narcolepsy type 1 trial TAK-861-2001 evaluating TAK-861 in 112 patients demonstrated statistically significant and clinically meaningful improvement in objective and subjective measures of wakefulness compared to placebo at week eight including on the primary endpoint Maintenance of Wakefulness Test (p < 0.001). 

Improvements in key secondary endpoints including Epworth Sleepiness Scale and weekly cataplexy rate were statistically significant and clinically meaningful, consistent with the primary endpoint. The majority of patients who completed the trial entered a long-term extension study. 

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 rapidly in the first half of its fiscal year 2024. At this time, Takeda does not plan to advance TAK-861 in narcolepsy type 2. 

Data are being further analyzed to determine next steps in orexin normal populations. Takeda is progressing multiple orexin agonists in patient populations with normal levels of orexin neuropeptides such as NT2 and other indications where orexin biology is implicated.

TAK-861 was generally safe and well tolerated in both trials. No treatment-related serious adverse events were reported. In addition, no cases of hepatotoxicity or visual disturbances were reported in the phase 2b trials or in the ongoing TAK-861 long-term extension trial.

“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,” says Sarah Sheikh, MSc, BM, BCh, MRCP, head of neuroscience therapeutic area unit and head of global development at Takeda, in a release. 

Results from both trials will be presented at an upcoming scientific congress.

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