ORZEYFUL (Oveporexton (TAK-861-3001)) - (FirstLight)

September 9, 2026: Takeda (NYSE: TAK) said the New England Journal of Medicine published results from the Phase 3 FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) trials of oveporexton (ORZEYFUL), an oral OX2R agonist, in adults with narcolepsy type 1.

FirstLight enrolled 168 participants across twice-daily 2 mg, 1 mg, and placebo arms; RadiantLight enrolled 105 participants in 2 mg and placebo arms. Over 12 weeks, oveporexton showed statistically significant improvements vs placebo across wakefulness, sleepiness, cataplexy, disease severity, and quality-of-life measures (all p<0.001), with effects seen at the earliest assessed timepoints and sustained through study end. Median weekly cataplexy reductions at week 12 were 79.0%-88.8% with oveporexton vs 27.7%-39.1% with placebo. More than 70% of treated patients reached mild severity on NSS-CT, 97% reported overall symptom improvement on PGI-C, and treated groups achieved normative thresholds on MWT and ESS. More than 95% of completers entered the long-term extension.

Safety was consistent with prior studies; common TEAEs were transient insomnia, urinary urgency/frequency, and excessive saliva, mostly mild to moderate. Takeda said oveporexton is approved in the U.S., China, and Japan, with additional regulatory submissions underway.