After Two Failures, Takeda Wins Approval for First Narcolepsy Drug, With $3.3 Billion in Peak Sales Expected

After two failures, Takeda Pharmaceutical has secured approval for the first-in-class drug for narcolepsy.

According to FiercePharma on the 6th (local time), the US Food and Drug Administration (FDA) approved Takeda’s Orzeyful (active ingredient: oveporexton) to treat adults with type 1 narcolepsy (NT1).

Unlike existing treatments, which alleviate symptoms, Orzeyful is the first drug to act directly on the underlying cause of the disease. It mimics the body’s cycle of orexin, a neuropeptide deficient in patients with narcolepsy, thereby regulating wakefulness, appetite and energy.

Julie Kim, Takeda’s chief executive officer (CEO), said in a statement, “We have opened a new chapter for the type 1 narcolepsy community by introducing an entirely new class of medicine that will redefine how the disease is managed.”

The approval was based on the results of two phase 3 clinical trials. In the studies, Orzeyful produced statistically significant improvements versus placebo in daytime sleepiness, cataplexy (the sudden loss of muscle tone) and quality of life. No serious treatment-related adverse events were reported during the trials, and the most common adverse events included insomnia and frequent urination.

Takeda expects Orzeyful to generate peak annual sales of $2 billion-$3 billion (approximately 3 trillion-4.5 trillion won) and is counting on it as a blockbuster drug. It is one of the key products expected to help protect Takeda’s performance as its flagship product Entyvio faces biosimilar competition.

The company plans to launch Orzeyful once the US Drug Enforcement Administration (DEA) completes its review of the drug’s controlled-substance classification. The review is expected to be completed within 90 days.

Orzeyful’s success follows two setbacks involving candidates with the same mechanism of action. Five years ago, Takeda discontinued two phase 2 trials of the orexin 2 receptor (OX2R) agonist TAK-994 because of liver toxicity concerns. Two years ago, it also abandoned development of another OX2R agonist, danavorexton (TAK-925), because of delays in trial enrollment.

Meanwhile, Takeda is also expecting approval for another first-in-class treatment in the third quarter of this year. Rusfertide, a blood disorder treatment licensed from Protagonist Therapeutics in 2024 for $300 million (approximately 450 billion won), is under FDA review. In addition, zasocitinib, a TYK2 inhibitor acquired through Takeda’s $4 billion (approximately 6 trillion won) purchase of Nimbus Therapeutics four years ago, is considered a promising product with expected peak sales of up to 9 trillion won.