Lemborexant (Dayvigo), a dual orexin receptor antagonist, won FDA approval to treat adult insomnia characterized by sleep onset or sleep maintenance difficulties, drugmaker .
The drug inhibits orexin signaling by binding to orexin receptor 1 (OX1R) and 2 (OX2R), the company said; when activated, OX1R suppresses REM sleep, and OX2R suppresses non-REM and REM sleep.
The FDA approval was based on research including two pivotal phase III studies that evaluated lemborexant in about 2,000 adult patients with insomnia. The trial tested 5- and 10-mg doses against zolpidem (Ambien) and placebo for 1 month in adults over age 55; studied the same doses against placebo for 6 months. Lemborexant bested placebo in sleep onset and sleep maintenance in both subjective and objective evaluations in these trials.
In both studies, the drug was not associated with rebound insomnia after treatment ended and showed no evidence of withdrawal effects after stopping at either dose.
The most common adverse reaction -- reported in 5% or more of patients treated with lemborexant and at least twice the rate of placebo -- in SUNRISE 1 and in the first 30 days of SUNRISE 2 was unwanted somnolence at 10% for the 10 mg dose, 7% for the 5 mg dose, and 1% for placebo.
The drug development program also included multiple safety studies assessing effects on postural stability, cognition, driving performance, and respiratory safety. Compared with placebo, nighttime dosing of both the 5 mg and 10 mg doses resulted in balance impairment at 4 hours. Lemborexant also was associated with dose-dependent worsening on measures of attention and memory versus placebo. Although the drug did not cause statistically significant impairment in next-morning driving performance compared with placebo, driving ability was impaired in some people who took lemborexant 10 mg.
Lemborexant 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," Lynn Kramer, MD, Eisai's chief clinical officer of the neurology business group, said in a .
The first orexin receptor antagonist, suvorexant (Belsomra), was approved to treat insomnia in 2014. Lemborexant will be commercially available in 5- and 10-mg tablets following scheduling by the DEA, which is expected to occur within 90 days, Eisai said.