Vanda Pharmaceuticals announced it received a decision letter from the FDA’s Center for Drug Evaluation and Research (CDER) stating that the supplemental New Drug Application (NDA) for Hetlioz (tasimelteon) for the treatment of jet lag disorder cannot be approved in its current form.

In its decision letter, the agency acknowledges the controlled clinical trials submitted by Vanda demonstrates positive efficacy signals. However, FDA determined that the data did not constitute substantial evidence of effectiveness for jet lag disorder.¹

The decision comes against the backdrop of previous legal proceedings, as in August 2025, the U.S. Court of Appeals for the District of Columbia Circuit set aside FDA’s earlier refusal to approve of Hetlioz for jet lag disorder. The court characterized Vanda’s evidence as “specific, reasoned, and rooted in evidence,” while labeling the FDA’s earlier review as “cursory,” noting statistically significant improvements on primary endpoints across trials.

Following the legal proceeding, in October 2025, the agency and Vanda agreed to a re-review of its supplemental new drug application (NDA) conducted under a collaborative framework agreement between the two parties. Under the agreement, the agency committed to an expedited re-review of the application by January 7, 2026, including considerations of narrower, sleep-focused indications.

How did FDA come to its decision?

FDA based its conclusion on its assessment of the controlled phase advance protocols used in the studies, specifically five-hour and eight-hour shifts in bedtime, claiming the shifts do not sufficiently reflect real-world jet travel.¹ The agency cited several aspects associated with air travel, such as reduced cabin pressure, physical constraints, noise, and lighting changes, as elements not captured by the study designs.¹

Vanda continues to dispute FDA’s interpretation, highlighting the widespread use of phase advance models in circadian rhythm research as established methods for simulating the core biological misalignment associated with eastward jet lag.¹ The company has maintained its stance, saying that the models isolate circadian disruption without introducing additional variables related to travel conditions. The company also cited data from studies involving both simulated protocols and actual transatlantic travel, saying the data demonstrates improvements in sleep duration, time to persistent sleep, and next-day alertness.¹

The company further noted that Hetlioz has an established safety profile which is supported by more than a decade of market experience in its approved chronic indications, including adverse events described as predominantly mild.

Vanda maintains that its submission met the statutory standard for substantial evidence of effectiveness on clinically relevant endpoints for jet lag disorder.

Although Vanda stated that it welcomed FDA’s engagement during the re-review process, the company does not believe the latest decision fully reflects the court’s concerns regarding engagement with the evidence, with Vanda saying it intends to continue discussions with the agency while considering additional steps related to the application.¹This includes the company saying it will “pursue all appropriate avenues” in order to advance the approval of Hetlioz.

Sources

1. Vanda Pharmaceuticals Announces Receipt of FDA Decision Letter on Hetlioz Supplemental New Drug Application for Jet Lag Disorder. Vanda Pharmaceuticals. January 8, 2026. https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-announces-receipt-of-fda-decision-letter-on-hetlioz-supplemental-new-drug-application-for-jet-lag-disorder-302656392.html