Takeda gets first OK for orexin narcolepsy drug, in China

China has become the first country to approve Takeda's first-in-class orexin agonist, oveporexton, for the sleep disorder narcolepsy.

The National Medical Products Administration (NMPA) has cleared oveporexton under the Orzeyful brand name for the treatment of narcolepsy type 1 in adults and adolescents aged 16 and over, ahead of regulators in the US and Japan, where it is under review. Filings in Europe are due later this year.

NT1 is a form of narcolepsy in which the sleep symptoms are accompanied by a sudden, brief loss of voluntary muscle control known as cataplexy. It is the most common, affecting 60% to 70% of all people living with the disorder.

Orzeyful – a selective orexin receptor 2 (OX2R) agonist – is designed to tackle a deficiency in orexin-producing neurons and compromised orexin signalling in the sleep disorder. In the pivotal FirstLight and RadiantLight trials, the drug achieved significant improvements in wakefulness, excessive daytime sleepiness, cataplexy, ability to maintain attention, overall quality of life, and daily life functions with the drug compared to placebo.

"For years, treatment options for narcolepsy type 1 have largely relied on symptomatic therapies to manage individual symptoms," according to Prof Han Fang, director of the Sleep Medicine Centre at Peking University People's Hospital.

"The approval of oveporexton represents a meaningful paradigm shift in narcolepsy type 1 treatment, signalling a transition from partial symptom management to a mechanism-driven approach that can help address the many symptoms evaluated in clinical studies and may support improvements in daily functioning and quality of life," he added.

China is the biggest market

China is the largest market for the new drug, with an estimated 700,000 people there living with NT1, according to Takeda. That compares with approximately 100,000 people in the US, 140,000 in Europe, and 200,000 in Japan, which has the highest prevalence rate per head of population globally.

The massive eligible patient population worldwide is driving big sales projects for Orzeyful, with Takeda previously suggesting peak sales could come in between $2 billion and $5 billion a year.

For Takeda, bringing oveporexton to market is a big achievement, given that its orexin agonist programme looked in jeopardy in 2021 when lead asset TAK-994 was abandoned for NT1 and NT2 – a form characterised by sleep symptoms only – after a liver toxicity signal emerged in phase 2 trials.

"As the first and only approved medicine to treat the broad spectrum of narcolepsy type 1, oveporexton has the potential to fundamentally change how the disease is managed," said Yan Liu, general manager of Takeda China.

"This milestone also marks an important step for Takeda China as we expand our local presence into neuroscience with the aim to advance care for disorders that have a profound impact on people and society," she added.

Other companies working on orexin agonists for narcolepsy include Alkermes, which has alixorexton (formerly ALKS 2680) in phase 3 trials for NT1 and NT2, and phase 2 for idiopathic hypersomnia, as well as Eisai, which has E2086 in mid-stage testing.

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