The dual orexin receptor antagonist demonstrated dose-dependent improvements in objective and subjective sleep outcomes, with a safety profile similar to placebo in children ages 10 to 17.
Key takeaways:
- A phase 2 study demonstrated a statistically significant, dose-dependent improvement in total sleep time for pediatric patients taking daridorexant compared to baseline.
- The safety profile of daridorexant at doses up to 50 mg remained similar to placebo, with no evidence of morning residual sleepiness, drug abuse events, or withdrawal symptoms.
- The trial enrolled children with a history of neurodevelopmental disorders, indicating potential new therapeutic applications for orexin signaling in these high-risk populations.
Idorsia Ltd announced positive top-line results from a phase 2 dose-finding study evaluating daridorexant, a dual orexin receptor antagonist (DORA), in pediatric patients aged 10 to under 18 years with insomnia disorder.
The primary objective of the phase 2 study was to characterize the dose-response relationship of daridorexant on objective total sleep time using polysomnography. The trial randomized 165 patients to receive 10, 25, or 50 mg of daridorexant, or a placebo, for a two-week treatment period.
Analysis of the primary endpoint showed a statistically significant (p=0.0185) dose-dependent improvement in total sleep time from baseline on day one. This was accompanied by additional dose-dependent improvements across multiple objective and subjective sleep parameters.
The trial enrolled children aged 10 to 11 years (21%) and 12 to 17 years (79%). This cohort included patients with a history of neurodevelopmental disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD).
“Pediatric insomnia is often chronic, and profoundly affects daytime functioning, mood, and cognitive and physical development,” says Katharina Lederer, MD, study physician and master of neuroscience at Advanced-Sleep-Research and principal investigator of the study, in a release. “These phase 2 findings are particularly exciting—treatment options for children and adolescents with insomnia remain extremely limited, and seeing robust efficacy without compromising safety constitutes a notable development in the field.”
The study confirmed the safety and tolerability profile of daridorexant in pediatric patients as young as 10. Even at the 50 mg dose—the recommended adult dose—the safety profile remained similar to placebo. Researchers noted no adverse events denoting drug abuse during treatment and no indication of withdrawal symptoms upon discontinuation. Additionally, visual analog scale estimates from patients and caregivers showed no morning residual sleepiness and indicated improved alertness.
“While behavioral treatments for insomnia are successful in alleviating insomnia symptoms in many cases, there remains a critical need for safe and effective insomnia medications, especially in high-risk populations such as children with autism and ADHD,” says Judith Owens, MD, MPH, professor emerita in the department of neurology at Harvard Medical School, in a release. “The daridorexant phase 2 results are compelling because they provide preliminary evidence of efficacy for pediatric insomnia alongside a reassuring safety profile.”
“These positive results show for the first time that daridorexant delivers strong, dose-dependent improvements in both objective and subjective sleep outcomes in children,” says Alberto Gimona, MD, head of global clinical development and medical affairs of Idorsia, in a release. “As the only DORA being investigated in children, daridorexant could become not only best-in-class for adults, but first-in-class for the pediatric population.”
Beyond sleep improvements, the results suggest that orexin signaling may play a broader role in children with neurodevelopmental disorders.
“We are not only helping young patients and their families—who urgently need evidence-based treatments when children suffer from chronic insomnia—but we are also seeing new signals that the orexin system may play an even more important role in neurodevelopmental disorders than previously understood,” says Martine Clozel, MD, pediatrician, chief scientific officer and head of research of Idorsia, in a release.
The study is part of an FDA-approved Pediatric Study Plan and an EU PDCO-approved Paediatric Investigation Plan. Idorsia plans to engage with health authorities to discuss next steps for pediatric insomnia and to explore a potential investigation pathway for children with neurodevelopmental disorders.
Daridorexant is currently marketed as QUVIVIQ for adult patients with insomnia in the US, Canada, and multiple European countries. Daridorexant for pediatric use remains investigational and is not approved or marketed in any country.
