Vanda Pharmaceuticals’ efforts to secure U.S. approval for Hetlioz as a treatment for jet lag have been set back once again after the Food and Drug Administration (FDA) rejected the company’s application. The FDA cited disagreements over the way Vanda tested the drug, leading to an 11% drop in the company’s share price to $7.60.
Hetlioz is already approved for several sleep disorders, but Vanda has sought a supplemental approval to market it for jet lag. In its Complete Response Letter, the FDA acknowledged “positive efficacy” in clinical trials but said that data did not demonstrate Hetlioz effectively treats jet lag syndrome, according to Vanda’s announcement on Thursday.
Vanda based its studies on phase advance protocols during Phase II and III trials completed in 2017 and 2018, where patient bedtimes were shifted by five and eight hours to simulate eastward travel. However, according to Vanda, the FDA found this approach was not “sufficiently analogous” to actual air travel conditions such as reduced oxygen pressure, physical confinement, noise, and lighting changes.
“Vanda respectfully disagrees with this interpretation,” the company stated. “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 statement continued: “These models reproducibly induce the essential features of jet lag without the confounders of variable travel conditions which are unrelated to jet lag.”
This rejection continues a years-long dispute between Vanda and the FDA over Hetlioz’s use for jet lag. Since 2019, when the agency first denied approval for this indication, Vanda has sought hearings with regulators and ultimately sued the FDA. In January 2024, a judge ruled in favor of Vanda, ordering either resolution of its supplemental new drug application or a hearing.
Instead of granting a hearing, the FDA issued another rejection. After appealing that decision, Vanda won again in August 2025 when a judge overturned the rejection. Following that ruling, both parties agreed in October 2025 to a “collaborative framework agreement” that called for expedited re-review by January 7, 2026.
Despite this latest setback from regulators, Vanda says it remains committed to seeking approval: The company said it “appreciates” working with the FDA on this application and will continue pursuing “all appropriate avenues” toward approval of Hetlioz for jet lag.
The relationship between Vanda and federal regulators has included other disputes as well. In April 2025, Vanda sued over restrictions on information provided to doctors about off-label uses of Hetlioz for jet lag; during that same month it also criticized what it described as "FDA bureaucrats" who rejected another drug candidate—tradipitant—for gastroparesis.
Meanwhile last week marked some positive news for Vanda: The FDA approved its motion sickness drug Nereus—the first new treatment authorized in that space in four decades.
