Vanda Pharmaceuticals’s drug, Hetlioz (tasimelteon), was approved Friday by the Food and Drug Administration (FDA) for the treatment of non-24-hour sleep-wake disorder, a chronic circadian rhythm disorder. This is the first approved treatment for the disorder, referred to as "Non-24," and is most commonly found in blind people who cannot perceive light — a daily cue that helps individuals synchronize their circadian system with the environment. About 70 percent of blind people live with Non-24.
Vanda, a Washington D.C.-based biopharmaceutical company, anticipates making Hetlioz commercially available in the second quarter of 2014. “Non-24-hour sleep-wake disorder can prevent blind individuals from following the normal daily schedule that we all take for granted,” said Dr. Eric Bastings, deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Hetlioz can improve the ability to sleep at night and to be active during the day.”
Non-24 causes two key symptoms: an inability to sleep or remain asleep at night and an overwhelming urge to sleep during the day. Though people who suffer from Non-24 often assume their symptoms are linked to a sleep disorder, the origin of their erratic sleep-wake patterns arise from a very different cause. A person’s master body clock running on its own natural rhythm is the true cause of Non-24. The fact is most of us have body clocks that run slightly longer than a strict 24 hours. Most people never suffer from Non-24 because environmental cues, primarily light, signal the brain to reset the master body clock. People who are blind, though, are unable to perceive light so this natural reboot never occurs, and their sleep patterns drift in and out of synch with the natural 24-hour routine. Additionally, people who have suffered head trauma may also find themselves unable to respond to natural cues and so the numbers of those affected by non-24 is estimated to range as high as 80,000 Americans.
The FDA reviewed Hetlioz under priority review, an expedited process intended for drugs that treat serious conditions. In scientific studies, Hetlioz showed evidence of its ability to reset the master body clock in the suprachiasmatic nucleus of the hypothalamus in the brain, which in turn helped to regulate the secretion of both melatonin and cortisol, natural hormones that impact metabolism and circadian rhythms. Treatment with Hetlioz was found to significantly increase nighttime sleep and decrease daytime sleep when compared to placebo in two clinical trials involving 104 totally blind participants with non-24 disorder. Use of the new drug resulted in synchronizing individual circadian rhythms with the external day/night cycle.
The most common side effects reported by participants in the two studies were headache, elevated liver enzymes in the blood, nightmares or unusual dreams, disturbed night’s sleep, upper respiratory or urinary tract infection, and drowsiness. The FDA recommended Hetlioz be taken at the same time every night before bedtime and activities should be limited after taking the drug, as it can impair activities that require complete mental alertness. Its general safety has been evaluated in over 1,300 individuals.
"Today's FDA approval of Hetlioz means that, for the first time, these patients have access to an approved, safe and effective treatment for their difficult debilitating disorder," said Dr. Steven W. Lockley, Division of Sleep Medicine, Brigham and Women's Hospital, in a press statement. Vanda President and CEO, Dr. Mihael H. Polymeropoulos, said the company is committed to facilitating access to the approved product.