FDA approves Takeda’s first-in-class narcolepsy drug

Takeda has secured FDA approval for the first drug to treat the underlying cause of narcolepsy type 1, with the company forecasting peak annual sales of between $2bn and $3bn as it seeks further regulatory approvals.

Known as Orzeyful (oveporexton), the therapy is an orexin receptor 2 agonist that restores a brain signal missing in people with narcolepsy type 1. Unlike existing treatments, it targets the underlying cause of the disease rather than simply treating its symptoms.

Narcolepsy is a chronic neurological disorder characterised by excessive daytime sleepiness, sudden muscle weakness known as cataplexy, sleep paralysis and vivid hallucinations.

For now, Orzeyful is approved only for adults with narcolepsy type 1 in the US. Its safety and efficacy have not yet been established in people younger than 18 years.

Orzeyful’s efficacy

The approval was backed by positive results from two pivotal clinical trials. In the FirstLight and RadiantLight studies, Orzeyful significantly improved patients’ ability to stay awake compared with placebo. The therapy also reduced cataplexy, sleep paralysis, hallucinations and disrupted night-time sleep. The most common adverse events included insomnia, increased urinary frequency, urinary urgency and increased salivation.

“The FDA approval of Orzeyful marks a new chapter for the narcolepsy type 1 community, as we introduce an entirely new class of medicine that will potentially redefine how this disease is managed and how people feel on treatment,” said Julie Kim, President and Chief Executive Officer, Takeda.

The company expects to launch Orzeyful in the US in November, subject to scheduling by the Drug Enforcement Administration.

Further approvals

The FDA’s decision follows Orzeyful’s clearance in China last month for adults and adolescents aged 16 years and older. The therapy also remains under review in Japan, while Takeda plans to file for approval in Europe later this year.

Although Takeda is first to market, competition is already building. Irish biopharmaceutical company Alkermes is progressing alixorexton through phase 3 trials, while Eli Lilly’s cleminorexton and Eisai’s ledasorexton are both in phase 2 development. Brain health company Lundbeck is also developing Lu AH69593, which is in phase 1b trials.