Phase 3 Results: Hetlioz Improves Sleep in Patients With Primary Insomnia

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Vanda Pharmaceuticals today shared new positive data from a phase 3 study on tasimelteon (Hetlioz) for the treatment of patients with insomnia.^1,2

Hetlioz is a dual melatonin 1 and melatonin 2 receptor agonist and circadian regulator that is currently approved for the treatment of non-24-hour sleep-wake disorder in adults and for the treatment of nighttime sleep disturbances in adults and children with Smith-Magenis Syndrome. Vanda is pursuing US Food and Drug Administation (FDA) approval for Hetlioz in the treatment of insomnia and jet lag disorder and is continuing to develop Hetlioz for the treatment of several other sleep disorders, including delayed sleep phase disorder and pediatric insomnia.

In the randomized, double-blind, placebo-controlled, multi-center study, investigators evaluated 20 mg or 50 mg Hetlioz vs placebo in 322 participants with primary insomnia over a 5-week double-blind treatment interval using polysomnography (PSG) measures of sleep. Participants underwent PSGs on nights 1, 8, 22, and 29.

Hetlioz met its primary endpoint, demonstrating a mean improvement in latency to persistent sleep (LPS) from baseline to the average of nights 1 and 8 of 44.9 minutes (20 mg) and 46.3 minutes (50 mg) vs 28.2 minutes (placebo) (P < 0.001). Improvements in LPS persisted through the follow-up time points (nights 22 and 29, P < 0.01). Hetlioz use was not associated with cognitive or mood changes, and neither rebound nor withdrawal effects were observed after discontinuation. Additionally, the currently approved dose of Hetlioz (20 mg) was able to reduce the amount of time it took to fall asleep for patients with chronic insomnia, and this clinically significant improvement was maintained with a reduction in sleep initiation of 52 minutes at 4 weeks.

As to safety and tolerability, Hetlioz was well-tolerated with no adverse next-day residual effects observed. The study authors noted that all current prescription drugs approved for insomnia have adverse effects including addiction, withdrawal, tolerance, and next-day residual effects such as driving impairment and sleep-driving.^3-5 Comparably, Hetlioz is a safe, effective and tolerable drug with no evidence of addiction, rebound insomnia, or next-day residual effects.⁶

Overall, Hetlioz improved sleep from the first night of treatment, and the effect continued for the duration of the study. The study was published in PLOS One.¹

“The results of the study strongly suggest that tasimelteon may be an effective therapeutic tool in the treatment of individuals with chronic sleep onset insomnia,” concluded the study authors.

References

1. Synnott NC, Polymeropoulos CM, Xiao C, et al. Melatonin agonist tasimelteon (HETLIOZ®) improves sleep in patients with primary insomnia: a multicenter, randomized, double-blind, placebo-controlled trial. PLOS One. 2025;20(9):e0332366.

2. Vanda Pharmaceuticals announces the publication in PLOS One of an article titled "Melatonin agonist tasimelteon (HETLIOZ®) improves sleep in patients with primary insomnia: A multicenter, randomized, double-blind, placebo-controlled trial". News release. September 25, 2025. Accessed September 25, 2025. https://vandapharmaceuticalsinc.gcs-web.com/node/16591/pdf

3. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349.

4. Lie JD, Tu KN, Shen DD, Wong BM. Pharmacological treatment of insomnia. P T. 2015;40(11):759-771.

5. Asnis GM, Thomas M, Henderson MA. Pharmacotherapy treatment options for insomnia: a primer for clinicians. Int J Mol Sci. 2015;17(1):50.

6. Torres R, Fisher M, Birznieks G, et al. Simulated driving performance in healthy adults after night‐time administration of 20 mg tasimelteon. J Sleep Res. 2021;31(1):e13430.