Vanda Pharmaceuticals (Nasdaq: VNDA) announced receipt of a decision letter from the US FDA, indicating stating that a supplemental New Drug Application (sNDA) for its circadian rhythm drug Hetlioz (tasimelteon) as a treatment of jet lag disorder cannot be approved in its current form.
The decision is the second time the FDA has declined to approve Hetlioz, after previously rejecting the drug in 2019. That decision was successfully disputed in the courts by Vanda, which led to a collaborative framework agreement between Vanda and the FDA established in October 2025, under which the agency agreed to re-review the long-running application by early January 2026.
Regulatory Rationale
According to the FDA’s decision letter from its Center for Drug Evaluation and Research (CDER), the agency acknowledged positive efficacy signals from Vanda’s controlled clinical trials. However, the regulator concluded that the data do not constitute substantial evidence of effectiveness for jet lag disorder, the principal concern being that trial models involving phase advance protocols (simulating 5-hour and 8-hour bedtime shifts) are not sufficiently representative of real-world jet travel — which includes additional variables such as reduced oxygen pressure, physical constraints, noise and light changes.
Vanda has publicly disagreed with the FDA’s interpretation, stating that phase advance models are widely accepted in circadian rhythm research as valid surrogates for the core circadian misalignment that underlies eastward jet lag and that the submitted dataset meets statutory standards for substantial evidence of effectiveness.
The jet lag regulatory path for Hetlioz has been protracted: previous FDA refusals were set aside by the US Court of Appeals for the DC Circuit in 2025, which criticized the agency’s earlier evaluation and ordered resolution of the application or a formal hearing. Despite that outcome, the FDA’s latest letter again stops short of approval.