Takeda's first-in-class narcolepsy drug claims FDA approval

Takeda's orexin agonist Orzeyful has been approved in the US to treat narcolepsy type 1 (NT1) in adults, becoming the first drug to treat the "full range" of symptoms in the sleep disorder, according to the FDA.

The US is the second country to approve the first-in-class orexin agonist after China, which cleared it for use in both adolescents aged 16 and over and adults last month. The drug is also under review in Japan, Takeda's home market, with filings in Europe due shortly.

Takeda said it is preparing for a commercial rollout of Orzeyful (oveporexton) in November but, as a novel central nervous system-acting drug, it will have to wait for assessment of its misuse potential and scheduling by the Drug Enforcement Administration (DEA) before launch. A DEA decision is due in the next three months.

"For too long, people with narcolepsy type 1 have had to manage a complex, lifelong neuropsychiatric condition with treatments that only address pieces of it," commented Tiffany Farchione, director of the Division of Psychiatry within the FDA's Center for Drug Evaluation and Research (CDER).

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 and other symptoms like sleep paralysis and hallucinations when on the edge of sleep or waking. It is the most common, affecting 60% to 70% of all people living with the disorder, and is believed to be caused by the loss of brain cells that produce orexin.

"This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole," said Farchione.

In the pivotal FirstLight and RadiantLight trials, Orzeyful achieved significant improvements in patients' ability to stay awake compared to placebo, along with improvements in cataplexy, sleep paralysis, hallucinations, and disrupted nighttime sleep. The most common side effects were insomnia, increased urinary frequency, urgency to urinate, and increased saliva production.

The FDA said use of the drug in people aged under 18 was not approved as its safety and efficacy in that age group has not been established.

Julie Kim, president and chief executive of Takeda, remarked that the approval "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."

It is an important new product for the Japan-headquartered group, which has predicted that sales could eventually reach between $2 billion and $5 billion a year.

Around 120,000 people are living with NT1 in the US, according to the Project Sleep patient advocacy group. Chief executive Julie Flygare – who has the disorder herself – said the approval is a "historic moment" and will help NT1 patients tackle symptoms that "reshape everyday life and extend far beyond what most people understand about the condition."

Other orexin agonists in the industry pipeline include Alkermes' alixorexton in phase 3 trials, Eli Lilly's cleminorexton and Eisai's ledasorexton in phase 2, and Lundbeck's Lu AH69593 in phase 1b.