Efficacy and Safety of TAK-861, an Oral Orexin Receptor 2 Agonist, in Individuals with Narcolepsy Type 1: Results from a Phase 2 Trial and Long-Term Extension Study Interim Analysis
Yves Dauvilliers1, Emmanuel Mignot2, Giuseppe Plazzi3, Gert Jan Lammers4, Harisha Kadali5, Ellie Stukalin5, Yaming Hang5, Yeting Du5, Anson Abraham5, Philipp von Rosenstiel5, Shinichiro Tanaka5, Melissa Naylor5, Alice Cai5, Tina Olsson5
1Sleep-Wake Disorders Center,Department of Neurology, Hopital Gui De Chaulliac, 2Stanford Center for Sleep Sciences and Medicine, 3Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio-Emilia, 4Department of Neurology, Leiden University Medical Centre, 5Takeda Development Center Americas, Inc
Objective:
To evaluate efficacy and safety of TAK-861 in patients with narcolepsy type 1 (NT1) enrolled in a phase 2 trial and its ongoing long-term extension (LTE) study.
Background:
NT1 is characterized by excessive daytime sleepiness and cataplexy and is associated with low cerebrospinal fluid orexin levels. The orexin receptor 2-selective agonist TAK-861 has wake-promoting effects and improves cataplexy-like symptoms in animal models of narcolepsy.
Design/Methods:
A completed 8-week, randomized Phase 2 trial (NCT05687903) assessed change from baseline to Week 8 in mean sleep onset latency on the Maintenance of Wakefulness Test (SOL-MWT; primary endpoint), ESS total score, weekly cataplexy rate (WCR), and occurrence of treatment-emergent adverse events (TEAEs). Participants enrolling into the LTE (NCT05816382) continued the same TAK-861 dose, or (phase 2 placebo arm only) were randomized to TAK-861 doses. LTE endpoints include occurrence of TEAEs (primary) and change in SOL-MWT, total ESS score, and WCR (secondary).
Results:
112 participants were randomized to TAK-861 or placebo (0.5mg BID n=23, 2mg BID n=21, 2mg/5mg n=23, 7mg QD n=23, placebo n=22); 104 continued into the LTE (0.5mg BID n=25, 2mg BID n=25, 2mg/5mg n=26, 7mg QD n=28). Compared with placebo, improvements from baseline to week 8 were achieved with TAK-861 doses in SOL-MWT (LS means change 12.5–25.4 vs -1.2 minutes, all p≤0.001), total ESS score (all p<0.01) and WCR (2mg BID and 2mg/5mg p<0.05). Improvements were maintained in the LTE (interim analysis). TEAEs occurred in 77.8% participants with TAK-861 in the phase 2 trial and 54.8% in the LTE. The most common TEAEs were urinary urgency/frequency and insomnia. There were no treatment-related serious TEAEs.
Conclusions:
In this Phase 2 study and LTE interim analysis, TAK-861 showed significant improvements in SOL-MWT, ESS and WCR versus placebo in participants with NT1 that were maintained up to at least 6 months and was well tolerated.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.