Vanda Pharmaceuticals: FDA says sNDA for hetlioz can’t be approved

Vanda Pharmaceuticals (VNDA) announced that it has received a decision letter from the U.S. FDA Center for Drug Evaluation and Research concluding that the supplemental New Drug Application for hetlioz for the treatment of jet lag disorder cannot be approved in its current form. This letter stems from CDER’s agreed re-review of the jet lag application under the October 1 collaborative framework agreement. The FDA acknowledged positive efficacy from Vanda’s controlled clinical trials, however, the FDA concluded that these data do not provide substantial evidence of effectiveness for jet lag disorder, primarily on the grounds that controlled phase advance protocols (5-hour and 8-hour bedtime shifts) are not sufficiently analogous to actual jet travel, which according to the FDA involves additional factors such as reduced oxygen pressure, physical constraints, noise, and lighting changes. “Vanda respectfully disagrees with this interpretation. 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. 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. 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.”