Japan approves first drug targeting root cause of narcolepsy type 1

The Japanese Ministry of Health, Labour and Welfare has approved Takeda Pharmaceutical‘s Orzeyful (oveporexton) for adults with type 1 narcolepsy (NT1).

The approval follows a similar decision by the U.S. Food and Drug Administration (FDA) earlier this month. The therapy has also been approved in China for people ages 16 and older with NT1.

According to Takeda, Orzeyful is the first approved therapy to target the disease’s underlying cause. The company said it will make the treatment available “as quickly as possible.”

NT1 is a chronic neurological disorder caused by a deficiency of orexin, also known as hypocretin, a chemical messenger that regulates wakefulness. Loss of orexin can cause excessive daytime sleepiness and a sudden loss of muscle tone known as cataplexy.

“Our discovery of the first orexin agonist is a successful representation of Japan-originated science that will directly impact people around the world living with narcolepsy type 1,” Julie Kim, president and CEO of Takeda, said in a company press release. “With the potential to redefine narcolepsy type 1 care, ORZEYFUL is the first validation of our broader orexin strategy, demonstrating how scientific innovation can create new possibilities for patients and drive future growth for Takeda.”

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Addressing the broad spectrum

“NT1 is a condition that can have a significant impact on patients’ lives around the clock,” said Yuichi Inoue, a professor at Tokyo Medical University. “Historically, treatment has primarily focused on managing individual symptoms. In recent years, advances in our understanding of the underlying pathophysiology [processes] of narcolepsy have led to the development of new therapeutic approaches.”

Unlike other treatments for NT1 that focus on controlling individual symptoms, Orzeyful is designed to address the broad spectrum of the disease.

The drug is an orexin receptor 2 (OX2R) agonist, meaning it activates the protein receptor OX2R to restore the missing orexin signal. By stimulating OX2R, Orzeyful is intended to promote wakefulness and ease a range of narcolepsy symptoms.

“I look forward to seeing a broader range of treatment options become available, helping physicians tailor treatment to the needs of each individual patient,” Inoue said.

The approval was supported by a clinical development program that included two Phase 3 clinical trials, FirstLight (NCT06470828) and RadiantLight (NCT06505031).

The two studies compared Orzeyful with a placebo for 12 weeks. Treatment significantly improved wakefulness and reduced cataplexy attacks, while also showing benefits for daily functioning, patient-reported quality of life, cognitive symptoms, and nighttime sleep.

Takeda said the Phase 3 program demonstrated significant improvements across the range of NT1 symptoms evaluated. Orzeyful was generally well tolerated, and its safety profile was consistent across clinical studies. The most commonly reported side effects included insomnia, urinary urgency (a sudden urge to urinate that can quickly become uncontrollable), increased urinary frequency, and excessive saliva.

“We credit our scientists in Japan who worked tirelessly to successfully discover a way to target the underlying orexin deficiency associated with narcolepsy type 1, a scientific feat that had never been achieved before,” said Asuka Miyabashira, president of Takeda’s Japan Pharma business unit. “It’s exciting for a biopharmaceutical company to discover, develop and commercialize an asset internally, and we are proud to have worked with our colleagues, healthcare providers and patient community to bring this new class of treatment to adults living with narcolepsy type 1 in Japan.”