Orexin, the ‘GLP-1 of neuroscience,’ emerges as next-generation contender in wakefulness drug market

Orexin drugs, dubbed the “GLP-1 of neuroscience,” are emerging as next-generation contenders in the sleep disorder treatment market.

According to Fierce Biotech, a U.S. biotechnology and pharmaceutical news outlet, on the 1st (local time), Japan’s Takeda Pharmaceutical received U.S. Food and Drug Administration (FDA) approval in August for Orexifil, a treatment for type 1 narcolepsy. The drug is the first approved medicine to mimic orexin, a wakefulness protein in the brain.

Experts believe orexin analogs could be used beyond narcolepsy to address a broad range of areas, including other sleep disorders, fatigue, cognition and mood. Luis de Lecea, a professor at Stanford University in the United States and co-discoverer of orexin, told Fierce Biotech, “It could provide many benefits in terms of attention or wakefulness,” adding, “It could be more effective than any drug currently available.”

Orexin was discovered independently in 1998 by de Lecea’s team and a team led by Masashi Yanagisawa. The peptide, produced by neurons in the hypothalamus, regulates not only sleep but all aspects of wakefulness. De Lecea described it as “the master switch for all wakefulness circuits.”

The link to narcolepsy was established through research by Emmanuel Mignot in the 1990s. Mignot identified the hypocretin-2 gene as the cause of narcolepsy in dogs and, for this work, shared the 2023 Breakthrough Prize with Yanagisawa.

Takeda’s orexin research also dates back to the late 1990s. Sarah Sheikh, Takeda’s head of global development, explained, “Understanding the root cause of the disease led to efforts to activate the receptor.” After successive failures to develop an intravenous drug and an oral drug, Takeda succeeded in developing Orexifil. Sheikh said, “It took only about 5 years from the first clinical trial to approval,” calling it “an unprecedented pace in neuroscience.”

Competition is also intensifying. U.S. GLP-1 market leader Eli Lilly acquired Centessa, a company specializing in sleep disorders, for $6.3 billion (about 8.8 trillion won) in March. Danielle Brill, an analyst at Truist Securities, said, “Lilly is betting that this class will become a large market,” adding, “It’s only a matter of time before more pharmaceutical companies follow.”

Ireland’s Alkermes is developing three orexin drugs, including alixorexton. Alkermes CEO Blair Jackson said, “Wakefulness is central to daily life and emotions,” adding, “It is becoming clear that orexin is also involved in inflammation and metabolism.”

Harmony Biosciences is developing BP-205, citing its safety and potential for once-daily dosing. Harmony CEO Jeffrey Dayno said, “A year ago, it was all about hypersomnia, but now the potential for broader applications in the central nervous system is attracting significant interest.”

Experts caution, however, that more clinical data are needed for orexin drugs to be used broadly. James Rowley, a professor at Rush Medical College in the United States, said, “The greatest potential right now is in the small niche market of patients with hypersomnia disorders,” but predicted that “even if it remains within the narcolepsy field, it will have an enormous impact.”