Cambridge, Mass. — Takeda said the New England Journal of Medicine has published results from two Phase 3 studies evaluating oveporexton, marketed as ORZEYFUL, in people with narcolepsy type 1.
Oveporexton is an oral orexin receptor 2 agonist designed to address the orexin deficiency that causes narcolepsy type 1. The drug is approved in the United States, China and Japan, with additional regulatory submissions underway.
“People living with narcolepsy type 1 face persistent symptoms across the day and night, which can impact many aspects of daily life,” said Emmanuel Mignot, M.D., Ph.D., Principal Investigator for the FirstLight Phase 3 study. “The newly published Phase 3 data reinforce the potential of oveporexton to transform how we approach narcolepsy type 1 in clinical practice, shifting from managing individual symptoms to treating the disease itself.”
The FirstLight study enrolled 168 participants who were randomized to receive twice-daily 2 mg oveporexton, twice-daily 1 mg oveporexton or placebo. The RadiantLight study enrolled 105 participants who received twice-daily 2 mg oveporexton or placebo.
Across the two studies, treatment with oveporexton produced statistically significant improvements compared with placebo in wakefulness, sleepiness, cataplexy, disease severity and quality-of-life measures over 12 weeks, Takeda said.
Median reductions in weekly cataplexy rates ranged from 79% to 88.8% among patients receiving oveporexton, compared with 27.7% to 39.1% for placebo at week 12.
More than 70% of treated participants reported mild disease severity according to the Narcolepsy Severity Scale, while 97% reported improvement in overall narcolepsy symptoms on the Patient Global Impression of Change scale.
“Leveraging the extensive research we conducted on the impact of narcolepsy type 1, we designed our comprehensive Phase 3 program to reflect the complexity of the disease and the experiences of those living with it,” said Sarah Sheikh, M.Sc., B.M., B.Ch., MRCP, Head, Neuroscience Therapeutic Area Unit and Global Development at Takeda. “The magnitude of effect seen across the full range of symptoms evaluated reinforces the potential of oveporexton to redefine how people feel on treatment. We are grateful to the patients, caregivers and healthcare providers who have participated in our studies and are thrilled to bring the first orexin agonist to the community.”
The most commonly reported treatment-emergent adverse events in the studies were transient insomnia, urinary urgency, urinary frequency and excessive saliva. Takeda said most events were mild to moderate and generally did not require medical intervention.
Oveporexton selectively stimulates the orexin receptor 2 to restore signaling associated with the orexin deficiency underlying narcolepsy type 1. It is approved for treating adults with narcolepsy type 1, also known as narcolepsy with cataplexy.
