Takeda's narcolepsy programme gets back on track

Takeda has said it intends to move quickly ahead with regulatory filings for oveporexton, its orexin agonist for sleep disorder narcolepsy, after a clean sweep of positive efficacy data in two phase 3 trials.

The Japanese drugmaker said that all primary and secondary endpoints were met in the two studies of oveporexton (TAK-861), which could become a first-in-class therapy for narcolepsy type 1 (NT1), a form where the sleep symptoms are accompanied by a sudden loss of voluntary control tone known as cataplexy.

The positive results are a major leap forward for Takeda's orexin programme, which looked in jeopardy in 2021 when lead asset TAK-994 was abandoned after phase 2 trials in type 1 and type 2 narcolepsy (a form with sleep symptoms only) revealed a safety concern.

The company pivoted to developing orexin receptor 2 agonist oveporexton in type 1 forms of the disease only, a decision that now looks to have paid off.

FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) are the first phase 3 trials to validate the mechanism of action of orexin agonists in narcolepsy, with significant improvements seen for Takeda's drug in wakefulness, excessive daytime sleepiness, cataplexy, ability to maintain attention, quality of life, and daily life functions compared to placebo.

In a statement, the drugmaker said that the new results "mark a major advancement toward transforming the standard of care by addressing the underlying cause of narcolepsy type 1." NT1 is thought to be caused by the loss of orexin-producing neurons in the brain.

"The comprehensive assessments from our phase 3 studies build on the transformative results we saw with our phase 2b study, with most participants reaching normative ranges and reporting clinically meaningful improvement across a broad range of symptoms at the end of the 12-week treatment period," said Takeda's R&D chief, Andy Plump.

"The positive results also reinforce the continued momentum for our late-stage pipeline, which we believe will deliver value to the patients we serve around the world," he added.

Takeda has highlighted oveporexton as one of its top near-term pipeline prospects, along with zasocitinib for psoriasis and polycythemia vera candidate rusfertide, which are also slated for regulatory filings this year or next.

The company is also investigating other orexin agonists in other indications, including TAK-360, an oral orexin 2 agonist initially being investigated for the treatment of narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and other sleep disorders.

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