The future of tasimelteon (Hetlioz) hit a snag as the US Food and Drug Administration (FDA) issued a Complete Response Letter (CLR) to Vanda Pharmaceuticals refuting data presented as clinically significant in treating jet lag disorder (JDL).
The CRL is a letter sent when the FDA determines they will not approve an application or abbreviated application in its present form as part of Vanda’s supplemental New Drug Application (sNDA).
On May 23, 2018, Vanda reported data that shows that jet lagged patients slept nearly 3 hours longer over the course of 3 nights following a transatlantic trip when treated with the drug than they did when they took the same trip untreated. While the data was consistent with Vanda’s jet lag simulation studies, the FDA indicated that the measures demonstrating improved sleep are of unclear clinical significance.
“We are deeply disappointed to have not received approval at this time, given our previous discussions with the FDA on this program,” Mihael H. Polymeropoulos, MD, Vanda's President and CEO, said in a statement. “Vanda remains committed to obtaining FDA marketing approval for tasimelteon in Jet Lag Disorder in order to address this significant unmet medical need.”
Currently, the melatonin receptor agonist drug is approved for treatment of non-24 Hour Sleep Wake Disorder both by the FDA and the European Medicines Agency.
Common adverse reactions associated with tasimelteon include headaches, increased alanine aminotransferase, nightmares or unusual dreams, and upper respiratory or urinary tract infections.
The risk of adverse reactions is greater in older patients than younger patients because the exposure to the drug increased by approximately 2-fold in elderly patients than younger patients.
Tasimelteon is also being evaluated for treating Smith-Magensis Syndrome and pediatric non-24-hour sleep-wake disorder. Vanda is also assessing the drug for treating delayed sleep phase disorder and for sleep disorders in patients with neurodevelopmental disorders.