The first in a new, potentially lucrative class of sleep medicines is now headed for market, with the Food and Drug Administration approving it on Wednesday as a treatment for the less common form of narcolepsy.
Developed by Japan-based Takeda Pharmaceutical, the medicine amplifies “orexin-2,” a protein that regulates key body functions like appetite, arousal and alertness. A pair of large clinical trials showed it was significantly better than a placebo at keeping patients awake as well as curbing the sudden muscle weakness that’s a trademark of “Type 1” narcolepsy. It was also generally well-tolerated by patients.
Takeda will sell the medicine under the brand name Orzeyful. While the company didn’t disclose the drug’s price, analysts at Jefferies guessed Orzeyful could cost anywhere from $142,000 per patient per year — on par with another sleep medication called Xywav — to north of $250,000. At the lower end of that range, analyst Stephen Barker predicts net annual sales of Orzeyful will peak at roughly $2 billion.
"For those of us living with narcolepsy type 1, symptoms reshape everyday life and extend far beyond what most people understand about the condition," said Julie Flygare, CEO of the patient advocacy group Project Sleep, in a statement from Takeda. As such, Orzeyful’s approval “is a historic moment that expands our treatment choices and gives me great hope for the future.”
Takeda CEO Julie Kim echoed those sentiments, calling the clearance a “new chapter for the narcolepsy type 1 community” that will “potentially redefine how this disease is managed and how people feel on treatment.”
“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,” Tiffany Farchione, director of the psychiatry division in the FDA’s main drug review office, said in a separate statement. “This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole.”
Since Orzeyful alters brain chemistry, and, importantly, neurological networks tied to “reward” feelings, it must now undergo a review from the Drug Enforcement Agency. Once the agency determines its scheduling classification — a process that could take up to 90 days — Orzeyful can officially launch.
A Takeda spokesperson said pricing information and approved access resources “will be communicated through the appropriate channels” when the drug becomes commercially available.
Other companies are racing to join Takeda in what’s predicted to be a multibillion-dollar market. The list includes fellow Japanese drugmaker Eisai along with Eli Lilly, which just entered the orexin space through a $6.3 billion buyout of Centessa Pharmaceuticals.
Ireland-headquartered Alkermes is the closest to Takeda, having recently begun a global, late-stage program evaluating its orexin-boosting drug “alixorexton” across both Type 1 and Type 2 narcolepsy. The company is also testing whether the drug can help patients with a related sleep disorder known as idiopathic hypersomnia.
Blair Jackson, Alkermes’ incoming CEO, sees these additional indications as a way to make up ground. In a June interview, he explained that the diagnosis “can sometimes be blurred” between two kinds of narcolepsies and idiopathic hypersomnia.
“You can imagine a situation where, when Takeda enters the marketplace with their drug, it can only be used in NT1. When that happens, payers are going to say to the doctors, ‘You must prove this patient has NT1.’ And you can do that in only a few ways,” Jackson said.
“Our goal is to come in and get approval across all three indications, so doctors don’t have to justify their diagnosis,” he added. That would create “flexibility and a lot of treatment options for those patients without having to deal with the payer every time you turn around.”
To Akash Tewari, a Jefferies analyst who covers Alkermes, the FDA’s Orzeyful decision “came in clean as expected.” Price and payer coverage “would be the key aspects to watch going into the launch,” he wrote in a note to clients.
