Takeda slams brakes on narcolepsy program, stopping 2 studies early in response to safety signal

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Takeda said it remains committed to orexin, pointing to the oral phase 1 candidate TAK-861 as an asset it is taking forward. (Takeda)

Takeda has hit the brakes hard on its narcolepsy program in response to a safety signal, stopping its two midphase clinical trials months before their planned completion dates. 

Japan-based Takeda saw the safety signal in phase 2 clinical trials of TAK-994, an oral orexin agonist designed to increase wakefulness. Takeda moved the prospect into a phase 2 clinical trial in narcolepsy patients early in 2020 before going on to start a second misphase study and pick up a breakthrough designation from the FDA this year.

Now, the program has come screeching to a halt. Takeda disclosed little in its statement, saying only that it has suspended dosing and stopped the phase 2 trials early as “an immediate precautionary measure” in response to a safety signal seen in the studies. 

According to ClinicalTrials.gov, the two studies were still enrolling subjects as of late last month with the goal of collectively recruiting more than 300 patients. ClinicalTrials.gov lists January and April 2022 as the completion dates of the two studies. Takeda said stopping the studies early will support “the timely interpretation of the benefit/risk profile of TAK-994” and identification of next steps.

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Details of the safety signal and whether it has implications for the broader class of orexin agonists are yet to emerge. Takeda’s interest in the target is underpinned by evidence linking narcolepsy to the loss of orexin neurons in the brain. Providing orexin replacement could increase wakefulness, making the receptor relevant to narcolepsy and other conditions such as obstructive sleep apnea.

Takeda put an intravenous orexin type-2 receptor agonist, TAK-925, through a clutch of early-phase clinical trials from 2017 to 2020 but has turned its attention to oral candidates in recent years. The safety signal throws the future of TAK-994 into doubt, but Takeda said it remains committed to orexin, pointing to the oral phase 1 candidate TAK-861 as an asset it is taking forward.