Vanda Pharmaceuticals has announced that the US FDA has rejected its supplemental New Drug Application (sNDA) for HETLIOZ (tasimelteon) for jet lag disorder "in its current form", despite positive trial results.
The decision comes from the FDA’s Center for Drug Evaluation and Research (CDER) as part of a re-review under the October 2025 collaborative framework agreement.
While acknowledging “positive efficacy from Vanda's controlled clinical trials,” the FDA said the data “do not provide substantial evidence of effectiveness for jet lag disorder,” citing concerns that phase advance sleep protocols used in the studies—5-hour and 8-hour bedtime shifts—“are not sufficiently analogous to actual jet travel,” which the agency says involves “reduced oxygen pressure, physical constraints, noise, and lighting changes.”
Vanda strongly disputes the FDA’s reasoning. “Phase advance models are widely accepted in circadian rhythm research as valid and reliable surrogates for simulating the core circadian misalignment underlying eastward jet lag—the primary driver of the disorder's hallmark symptoms per ICSD-3 criteria,” the company said.
“These models reproducibly induce the essential features of jet lag without the confounders of variable travel conditions which are unrelated to jet lag. The convergent evidence from Vanda's studies including simulated and actual transatlantic travel demonstrates tasimelteon's meaningful benefits on sleep duration, latency to persistent sleep, and next-day alertness.”
The company also highlighted the drug’s safety record. “Tasimelteon's safety profile is also well-established, with predominantly mild adverse events and a market experience of over 10 years in chronic approved indications. Vanda maintains that the submitted dataset meets the statutory standard for substantial evidence of effectiveness on clinically relevant endpoints, for jet lag disorder.”
The decision comes after a pivotal court ruling. In August 2025, the D.C. Circuit set aside a prior FDA refusal, describing Vanda's evidence as “specific, reasoned, and rooted in evidence” and the FDA’s earlier review as “cursory,” while noting “statistically significant improvements on primary endpoints across trials.”
Following that ruling, Vanda and the FDA entered a collaborative framework in October 2025, with the agency agreeing to an expedited re-review by January 7, 2026.
Vanda responded to letter by emphasizing its commitment to ongoing dialogue with regulators.
“Vanda appreciates the FDA's engagement but believes the current decision does not fully reflect the collaborative spirit or address the Court's concerns regarding meaningful engagement with the evidence. Vanda remains committed to working constructively with the FDA while pursuing all appropriate avenues to advance approval of HETLIOZ for jet lag disorder and make this important therapy available to travelers.”
