Following promising Phase IIb studies, Takeda will advance its oral ORX2 agonist TAK-861 into Phase III studies for narcolepsy type 1, while nixing the candidate’s development in narcolepsy type 2.
Pictured: Takeda’s office in Cambridge, Massachusetts/iStock, hapabapa
Takeda on Thursday announced that it will launch global Phase III trials of its investigational oral ORX2 agonist TAK-861 in narcolepsy type 1 in the first half of fiscal year 2024 and abandon the candidate’s development in narcolepsy type 2.
The pipeline decisions come after Takeda released positive topline data from a Phase IIb trial of TAK-861 in narcolepsy type 1 (NT1), which is mainly characterized by the loss of orexin neurons. In the study, Takeda’s candidate induced “statistically significant and clinically meaningful” improvements in both objective and subjective metrics of wakefulness versus placebo.
After eight weeks, patients treated with TAK-861 saw significantly better outcomes in the Maintenance of Wakefulness Test—the trial’s primary endpoint—with a p-value of less than 0.001, according to Takeda. TAK-861 also outperformed placebo in terms of key secondary endpoints, including the Epworth Sleepiness Scale and Weekly Cataplexy Rate.
In terms of safety, the Phase IIb trial did not document any treatment-related serious adverse events. There were also no instances of hepatotoxicity or visual disturbances both in the mid-stage study and in the ongoing long-term extension trial.
Most of the study’s participants opted to enter into the long-term extension phase.
Sarah Sheikh, head of global development at Takeda, said in a statement that the company is “thrilled” about these results, which will allow it to “rapidly initiate Phase III trials this year.”
However, Takeda “does not plan to advance TAK-861 in [narcolepsy type 2],” according to its announcement, though the company did not explicitly reveal why it is discontinuing TAK-861 in this indication.
Takeda will continue to analyze the data from both trials to determine the next steps for its narcolepsy programs, particularly in populations with normal orexin levels. The company also plans to share data from both studies at an upcoming scientific meeting.
TAK-861 has the potential for Takeda to bounce back from a previously-stalled narcolepsy program, Elena Koundourakis, who leads the company’s orexin program, told BioSpace in January.
In October 2021, Takeda had to put its previous Phase II oral narcolepsy hopeful—dubbed TAK-994—on ice due to safety concerns. The company at the time did not reveal what specific safety issues arose, but the candidate has since been removed from Takeda’s pipeline.
“We weren’t sure if, with the oral TAK-994 at that time, [we could] address all the symptoms,” Koundourakis told BioSpace, adding that it was the first time the company shifted from an intravenous to an oral narcolepsy drug. Still, Takeda kept backup programs so when TAK-994 was discontinued, “everybody working on 994 started working on TAK-861,” she added.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
