Oveporexton demonstrates therapeutic potential in narcolepsy type 1

Treatment with the investigational oral orexin receptor 2–selective agonist oveporexton appears to yield improvements in wakefulness, sleepiness, and cataplexy in individuals with narcolepsy type 1, according to the results of a phase II study.

A total of 122 participants with narcolepsy type 1 were randomly assigned to receive either once- or twice-daily oveporexton (n=90) or placebo (n=22). In the oveporexton group, 23 participants received the drug at 0.5 mg twice daily, 21 at 2 mg twice daily, 23 at an initial dose of 2 mg followed by 5 mg daily, and 23 at 7 mg once daily.

Researchers measured the mean change in average sleep latency on the Maintenance of Wakefulness Test (MWT) (range 0–40 minutes; normal ≥20) at week 8 as the primary study endpoint. Secondary endpoints included the Epworth Sleepiness Scale (ESS) total score (range 0 to 24; normal ≤10), the weekly cataplexy rate, and the occurrence of adverse events.

At week 8, sleep latency on the MWT significantly improved from baseline across the oveporexton groups vs the placebo group (mean changes, 12.5, 23.5, 25.4, and 15.0 vs −1.2 min; p≤0.001 for all comparisons).

Likewise, sleepiness outcome was more favourable in the oveporexton groups vs the placebo group, as evidenced by greater reductions in the ESS total score at week 8 (−8.9, −13.8, −12.8, and −11.3 vs −2.5; p≤0.004 for all comparisons).

Meanwhile, the weekly incidence of cataplexy at week 8 was significantly lower in the oveporexton groups at the 2-mg-twice-daily and 2-mg-followed-by-5-mg-daily doses vs the placebo group (3.14 and 2.48 vs 8.76; p<0.05 for both comparisons).

In terms of safety, the most frequently reported adverse events among oveporexton-treated patients were insomnia (48 percent, with most cases resolved within 1 week), urinary urgency (33 percent), and urinary frequency (32 percent). No hepatotoxic effects were observed.