The U.S. Food and Drug Administration (FDA) approved Eisai’s Dayvigo (lemborexant) for adults with sleep onset and/or sleep maintenance in adults—insomnia, in other words. Before it can hit the market in the U.S., the U.S. Drug Enforcement Agency (DEA) will determine scheduling, which is expected within 90 days.
Lemborexant binds to orexin receptors, OX1R and OX2R, acting as a competitive antagonist. This appears to treat insomnia via antagonism of orexin receptors, because the orexin neuropeptide signaling system plays a part in being awake.
The clinical trials the approval is based on suggested the drug was effective for treating primary insomnia but may also be effective for insomnia associated with other diseases, such as depression. It is also being evaluated in a Phase II trial in patients with ISWRD (irregular sleep wake rhythm disorder), associated with mild to moderate Alzheimer’s dementia.
“Insomnia disorder is a chronic condition that has a variety of potential negative impacts and long-term consequences for health and well-being,” said Russel Rosenberg, principal investigator in the Dayvigo clinical trial and former chairman of the board of the National Sleep Foundation. “The clinical trials provide evidence that Dayvigo may improve patients’ ability to fall asleep and stay asleep.”
The approval was built on two pivotal Phase III trials, SUNRISE 2 and 1. They evaluated Dayvigo to comparators for up to one month and Dayvigo to placebo for six months, respectively. Together, they evaluated about 2,000 adults with insomnia. The trials showed statistically significant superiority on sleep onset and maintenance compared to placebo in measures both subjective and objective.
SUNRISE 2’s primary efficacy endpoint was the mean change from baseline to end of treatment at six months for patient-reported sleep onset latency (sSOL). sSOL is defined as the estimated minutes from the time the patient attempted to fall asleep to actually falling asleep. Both the 5 mg and 10 mg disease demonstrated statistically significant superiority in sSOL.
SUNRISE 1 was a short-term study of one month evaluating adults women age 55 and older and men 65 and older who met the DSM-5 criteria for insomnia disorder. Patients received either 5 mg or 10 mg of Dayvigo or a placebo or active comparator once a night. The primary efficacy endpoint was mean change in latency to persistent sleep from baseline to end of treatment measured by overnight polysomnography (PSG). The two drug doses showed statistically significant superiority on the primary endpoint compared to placebo.
The most common adverse reaction was somnolence. Additional studies to evaluate the safety of the drug were also conducted, looking at the effects of the drug on postural stability (the ability to maintain an upright position), cognitive performance and a next-morning driving study. The studies didn’t show any meaningful effect on memory or postural stability. The company did warn that patients on the 10 mg dose could have some driving difficulties the next day.
The drug has also been submitted to Japan and Cana regulatory authorities.
“We believe the approval of Dayvigo is particularly exciting because it is the first FDA-approved medication to report safety data over a 12-month period along with sleep onset and sleep maintenance efficacy data over a six-month period in a pivotal clinical study,” said Lynn Kramer, chief clinical officer, Neurology Business Group, Eisai. “We look forward to making this new therapeutic option available to the millions of patients who suffer with insomnia.”
