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.

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.

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.

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.