Daridorexant: First Approval

  title={Daridorexant: First Approval},
  author={Anthony Markham},
  pages={601 - 607}
Daridorexant (Quviviq™; Idorsia Pharmaceuticals Ltd.) is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist (DORA) being developed for the treatment of insomnia. It was selected from a pool of drug candidates on the basis of an expected effect duration of ≈ 8 h at a dose of 25 mg, with a half-life intended to minimize residual effects that might impair daytime functioning. Based on the results of two pivotal phase III trials, daridorexant was recently… 
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Daridorexant for the Treatment of Insomnia.

Daridorexant is a dual orexin type 1 and types 2 (OX1 and OX2) receptor antagonist that was recently approved by the US FDA for the treatment of adults suffering from insomnia and was shown to be effective in reducing insomnia symptoms, increasing daytime functioning, and improving the overall quality of sleep.

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

In older patients with insomnia, as in younger patients, the efficacy of daridorexant is maximal on night-time and daytime variables at the higher dose of 50 mg, and older patients particularly require this dose to improve daytime functioning.

Orexin Receptor Antagonists and Insomnia

We review recent evidence on the use of orexin receptor antagonists (ORAs) for treating insomnia. We evaluate studies on five dual ORAs and one selective ORA. Research on suvorexant in recent years



Effect of gastric pH and of a moderate CYP3A4 inducer on the pharmacokinetics of daridorexant, a dual orexin receptor antagonist

The purpose of this study was to assess the effect of an increased gastric pH on daridorexant pharmacokinetics (PK) and the extent of interaction when daridexant is co‐administered with a moderate CYP3A4 inducer.

The dual orexin receptor antagonist daridorexant does not affect the pharmacokinetics of the BCRP substrate rosuvastatin

The results showed that concomitant administration of 25 mg daridorexant o.d. at steady state did not affect the exposure parameters of rosuvastatin in a relevant way, as indicated by the ratios of geometric means (GMRs) for both Cmax and AUC0‐∞.

Impact of Daridorexant, a Dual Orexin Receptor Antagonist, on Cardiac Repolarization Following Bedtime Dosing: Results from a Thorough QT Study Using Concentration-QT Analysis

Daridorexant does not impair cardiac repolarization evidenced by absence of relevant QT prolongation at therapeutic and supratherapeutic doses and its pharmacokinetics were consistent with previous data.

Effect of Liver Cirrhosis on the Pharmacokinetics, Metabolism, and Tolerability of Daridorexant, A Novel Dual Orexin Receptor Antagonist

A dose adjustment is not required in Child–Pugh A patients, while avoidance of daridorexant in patients with Child-Pugh C cirrhosis is recommended, a premise that dual orexin receptor antagonists may fulfill.

Abuse potential assessment of the new dual orexin receptor antagonist daridorexant in recreational sedative drug users as compared to suvorexant and zolpidem.

In this large, valid human abuse potential study, daridorexant showed dose-related drug-liking among recreational sedative drug users with lower effects at the highest phase-3 dose, and similar effects at higher doses compared to supratherapeutic doses of suvoreXant and zolpidem.

Pharmacological Interactions between the Dual Orexin Receptor Antagonist Daridorexant and Ethanol in a Double-Blind, Randomized, Placebo-Controlled, Double-Dummy, Four-Way Crossover Phase I Study in Healthy Subjects

Coadministration with ethanol produced a numerically greater impairment on saccadic peak velocity, body sway, visual analog scale (VAS) alertness, VAS alcohol intoxication, smooth pursuit, and adaptive tracking compared with daridorexant alone, which was generally well tolerated without serious adverse events.

Accelerated Development of the Dual Orexin Receptor Antagonist ACT‐541468: Integration of a Microtracer in a First‐in‐Human Study

Clear dose‐related effects on the central nervous system were observed at ≥25 mg, indicating a suitable PK‐PD profile for a sleep‐promoting drug, allowing for rapid onset and duration of action limited to the intended use.

Orexin receptors: pharmacology and therapeutic opportunities.

As the orexin system mainly promotes arousal, these new compounds will likely improve insomnia without incurring many of the side effects encountered with current medications.