The dual orexin receptor antagonist notably demonstrates a positive benefit-risk balance for patients
New data from an analysis of 2 Phase 3 trials show daridorexant for insomnia to have a positive benefit-risk balance for patients.
“The efficacy and safety of daridorexant, a dual orexin receptor antagonist intended to treat insomnia, was demonstrated in two placebo-controlled phase III trials,” wrote the study investigators, led by Sebastian Heidenreich, PhD, of Evidera.
“Both pivotal trials included instruments for eliciting treatment preferences of enrolled patients, to interpret the trial findings from their perspective using a patient-centered benefit-risk assessment (pBRA),” they noted
The team assessed data from a discrete choice experiment (DCE), which was developed according to digital ethnographies and qualitative interviews. They noted that the DCE was pre-tested in qualitative and quantitative pilots prior to inclusion in the Phase 3 studies.
The investigators then analyzed this data using a mixed logit model, which took into account heterogeneity of preferences, and obtained relative attribute importance and maximum acceptable risk of abnormal thoughts and behavioral changes.
All patients in the clinical trials valued all 7 of the aforementioned outcomes—however, daytime functioning (RAI = 33.7%) and avoiding treatment withdrawal (RAI = 27.5%) were considered the most important outcomes.
Nonetheless, patients were willing to trade a 18.8% increased risk (P < .001) of abnormal thoughts and behavioral changes for improvements in daytime functioning from difficulty or restricted functioning.
“The pBRA suggested that both daridorexant 50 mg and 25 mg were significantly preferred (P< 0.001) over placebo, and 50 mg was significantly preferred (P<0.001) over 25 mg, even after accounting for uncertainty in clinical outcomes and preferences,” Heidenreich and colleagues reported.
They noted these findings suggested a positive benefit-risk balance across both doses.
“Overall, the preference data allowed for an innovative interpretation of the trial data from patients’ perspective,” they wrote.
The study, "A Benefit-Risk Assessment Of Daridorexant For The Treatment Of Insomnia Using Patient Preference Data From Two Phase 3 Trials," was published online in Sleep.