With a positive classification from the DEA paving the way for Orzeyful’s U.S. launch on Thursday, Takeda is charting new territory in the treatment of narcolepsy type 1 as it de-risks other assets in its budding orexin franchise in parallel.
Takeda won FDA sign-off on its first-in-class oral orexin receptor 2 (OX2R) agonist Orzeyful (oveporexton) in early August, though it needed to wait on a scheduling decision from the U.S. Drug Enforcement Administration (DEA) before it could proceed with launch.
The medicine has now been tagged as Schedule IV—a category inclusive of drugs the DEA has determined to have a “low potential” for abuse and risk of dependence—and in turn clearing the “last hurdle” before rollout, analysts at Jefferies wrote in a note to clients Wednesday. The categorization also places the new-to-market Orzeyful “below the oxybates and well below stimulants” in terms of DEA scheduling hierarchy, the analyst team said.
Oxybate-based drugs, classed as Schedule III, cover popular narcolepsy treatments like Jazz Pharmaceuticals’ Xyrem and Xywav and Alkermes’ Lumryz, which was originally developed by Avadel. These treatments are cleared to treat excessive daytime sleepiness and cataplexy, or sudden loss of muscle strength while awake, which are prominent symptoms of narcolepsy.
Takeda hopes that Orzeyful, on the other hand, can set itself apart by attacking the condition at its source through mimicry of the body’s orexin cycle. Aside from that novel approach to treatment, the Schedule IV classification should also accelerate uptake by doctors and patients, given a lower potential risk for misuse, the Jefferies team said.
On Thursday, Takeda announced that Orzeyful has now officially launched in the U.S.
In shaping its pitch for the drug, Takeda noted that the “persistent 24-hour nature” of narcolepsy type 1 (NT1) goes well beyond just daytime sleepiness and frequently takes a toll on how people plan their days and navigate their lives.
“We work for decades toward the defining moments that have the potential to make a real difference for patients,” Rhonda Pacheco, president of Takeda’s U.S. business unit, said in a statement.
“Bringing Orzeyful, a first-in-class medicine, to people living with narcolepsy type 1 in the U.S. is one of those moments,” she continued. “We’re incredibly proud to be here, and equally focused on what comes next: supporting care and access for patients prescribed Orzeyful.”
Takeda noted in its release that Orzeyful will be dispensed in the U.S. via Evernorth Health Services’ Accredo Specialty Pharmacy.
Fierce has reached out to the company, asking about the drug’s price and Takeda’s broader access strategy.
NT1 represents a major commercial opportunity, affecting some 120,000 people in the U.S., and Takeda has previously pinned Orzeyful peak sales projections at $2 billion to $3 billion. As the Jefferies team sees it, the drug could reach sales of 3.9 billion Japanese yen ($24 million) during the company’s 2027 fiscal year, before scaling to 51 billion yen ($319 million) in fiscal year 2028 and 392.6 billion yen (nearly $2.5 billion) by fiscal year 2034.
The analysts flagged Orzeyful’s DEA scheduling as a key potential advantage, noting that doctors and patients are “wary of controlled drugs.” With a Schedule IV tag, doctors will likely be “more willing [to] prescribe Orzeyful and patients more willing to start treatment,” they argued.
Critically, the positive scheduling bodes well for the broader class of orexin agonists, too, where Takeda is investing heavily. The Jefferies team speculated that “since the DEA tends to schedule drugs with the same mechanism consistently, we now see Schedule IV as the most likely outcome for TAK-360 and Takeda's other orexin agonists.”
That will be key, they argued, as Takeda pursues development targets across a wider range of symptoms, where “a lenient schedule will be even more significant commercially.”
In the case of TAK-360, Takeda is testing the orexin medicine across not only NT1, but also narcolepsy type 2 and idiopathic hypersomnia.
Bigger picture, Orzeyful is one of three new drugs Takeda hopes will pick up the sales slack from IBD blockbuster Entyvio, which is staring down the prospect of biosimilar competition.
The company passed another milestone on that quest this summer when it won FDA approval for rusfertide, christened Mimrylo, bringing a new mechanism of action to bear against the blood disorder polycythemia vera (PV).
The third piece of the puzzle comes in the form of zasocitinib, which is up for an FDA decision in moderate-to-severe plaque psoriasis in 2027’s first quarter.
All three medicines have “peak sales potential of several billion dollars,” Jefferies noted.