In a saga that has spread over seven years, the FDA has again rejected Vanda’s bid to expand the label for Hetlioz to treat jet lag disorder.
The new thumbs-down came Wednesday, three months after the FDA said it would re-review its original rejection from 2019. The agreement to re-review came only after a Washington D.C. appeals court in August of last year set aside an FDA decision to deny Vanda a hearing and a re-review.
In Wednesday’s CRL, the FDA acknowledged the “positive efficacy” of Hetlioz demonstrated in its clinical trials, Vanda said. But the U.S. regulator ruled that the trials protocols were not “sufficiently analogous to actual jet travel,” the company said. Factors of jet travel cited by the FDA that complicate the assessment include reduced oxygen pressure, physical constraints, noise and lighting changes.
“Vanda respectfully disagrees with this interpretation,” the company wrote in its release. “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.”
Vanda added that the data package it submitted “meets the statutory standard for substantial evidence of effectiveness on clinically relevant endpoints, for jet lag disorder.”
With the news, Vanda’s share price decreased by 12% by publication time Thursday morning.
“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,” the Washington, D.C.-based company added. “Vanda remains committed to working constructively with the FDA while pursuing all appropriate avenues to advance approval of Hetlioz for jet lag disorder.”
This is not yet a done deal for Vanda. Since the case is "under remand" by the D.C. Court of Appeals for further proceedings, the FDA now "would need to proceed with a formal hearing," the company said in response to a request for more information.
When the FDA rejected Vanda's jet lag disorder application in 2019, the agency took issue with the way the company tried to show longer sleep durations in a small study of people who flew from the U.S. to the U.K. Overall, 13 patients who received Hetlioz slept nearly three hours longer than 12 peers in a control cohort.
Vanda ultimately disputed the decision and requested an FDA hearing in July 2022. The company explained that the FDA “privately” agreed to the hearing but failed to publish a notice in the Federal Register, which stonewalled the hearing process. The company kicked things up a notch when it sued the agency in September 2022.
The FDA originally signed off on Hetlioz in 2014 as a treatment for Non-24-Hour, a sleep-wake disorder. Then in 2020, Vanda gained a label expansion for Hetlioz for Smith-Magenis syndrome.
Sales of Hetlioz have been in decline after peaking at $173 million in 2021. The drug generated $77 million in sales in 2024 and $55 million through the first three quarters of 2025.
Less than two weeks ago, Vanda scored an FDA approval for motion sickness pill, Nereus. The decision came 15 months after the FDA rejected the oral neurokinin-1 (NK-1) receptor antagonist to reduce nausea and vomiting in patients with the digestive disorder gastroparesis.