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Potential insomnia treatment shows promise
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Lemborexant, a small molecule compound that obstructs orexin-signaling by binding to orexin receptors, showed many insomnia-related benefits, according to a press release and data presented at SLEEP.
The American Academy of Sleep Medicine estimates that approximately 30% of adults have insomnia symptoms. Less than 10% of adults have chronic insomnia.
“There is an unmet medical need for effective, well-tolerated pharmacological treatments for insomnia disorder that are studied over the long-term,” Mikko Kärppä, MD, PhD, of University of Oulu in Finland’s Research Medical Center and colleagues wrote in a study abstract.
Efficacy, tolerability
Margaret Moline, PhD, executive director of Eisai Inc.’s neurology working group, conducted a pooled analysis of 402 men and 1,291 women older than 18 years with insomnia who received either zolpidem tartrate extended-release, placebo, 5 mg of lemborexant or 10 mg of lemborexant for either 1 month or 6 months.
Researchers found that vs. placebo, both doses of lemborexant significantly reduced subject-reported sleep onset latency in both sexes (P < .05) and significantly and greatly reduced wake after sleep onset in women (P < .0001) at 7 days and 1 month. In addition, the 5-mg dose led to significant decreases in wake after sleep onset in men after 7 days (P .00001) and the 10-mg dose led to significant decreases in this same condition in men after 1 month (P = .0032).
Moline and colleagues also reported that regardless of sex, the overall incidence of treatment-emergent adverse events was low and the most common adverse event (somnolence) was consistent.
The same researchers found in another study, based on 1,006 patients within the same cohort, that those who received lemborexant had increased time in all stages of REM sleep, and lemborexant was superior to zolpidem tartrate extended-release in total sleep time, non-REM sleep and stage N2 sleep.
Insomnia severity
Tom Roth, PhD, of the department of sleep disorders at the Henry Ford Hospital in Detroit, and colleagues conducted another pooled analysis using the sleep stages cohort in the Moline et al study. The mean Insomnia Severity Index scores of the patients in the study ranged from 19 to 19.3 at baseline.
Researchers found that after 1 month, mean Insomnia Severity Index scores dropped by seven or more points in 47.3% of patients receiving 5-mg lemborexant, in 47.8% of patients receiving the 10-mg dose and in 33.6% of those receiving placebo. Also at 1 month, the percentage of patients whose scores dropped below 10 was 33% of those receiving the 5-mg dose, 33.4% of those receiving the 10-mg dose and 20.3% of those taking placebo (P < .0001).
Safety
In another study, Kärppä and colleagues randomly assigned 959 patients in an approximate 1:1:1 ratio to receive either placebo, 5 mg of lemborexant or 10 mg of lemborexant for 6 months.
They found that among patients receiving lemborexant, those who received the 5-mg dose (61.1%) had more treatment-related adverse events than those receiving the 10-mg dose (59.6%). Most adverse events were considered mild or moderate and consisted of somnolence (5-mg dose, 8.6%; 10-mg dose, 13.1%), headache (5-mg dose, 8.9%; 10-mg dose, 6.7%), influenza (5-mg dose, 4.8%; 10-mg dose, 5.1%), upper respiratory tract infection (5-mg dose, 4.1%; 10-mg dose, 3.5%), back pain (5-mg dose, 3.8%; 10-mg dose, 2.9%) and fatigue (5-mg dose, 3.8%; 10-mg dose, 3.5%).
There were no deaths and no clinically significant findings or differences among patients’ electrocardiograms, laboratory tests, safety profiles, vital signs or weight.
Impact on obstructive sleep apnea
Jocelyn Chang, MD, the director of Eisai’s Clinical Research Neuroscience department, and colleagues looked at the impact of two 8-night periods of placebo or 10 mg of lemborexant, separated by a 14-day washout, on respiratory measures in 39 patients with obstructive sleep apnea, the majority of whom were white and female. At baseline, the mean age of all participants was 57.2 years, mean SpO2 scores were 94.8% and mean Apnea-Hypopnea Index was 9.
Researchers found no significant difference in either measure after single or multiple 10-mg doses vs. placebo, leading them to conclude “lemborexant demonstrated respiratory safety” in the cohort in the measures studied.
According to a press release, lemborexant is being developed by Eisai. The drug’s PDUFA date is set for Dec. 27, 2019. – by Janel Miller
References:
Cheng J, et al. Respiratory safety of lemborexant in healthy adult and elderly subjects.
Kärppä M, et al. Lemborexant treatment for insomnia: 6-month safety.
Moline M, et al. Efficacy and tolerability of lemborexant in female and male subjects with insomnia.
Moline M, et al. Effect of lemborexant on sleep architecture in older adults with insomnia disorder,
Roth R, et al. Lemborexant treatment for insomnia in phase 3: impact on disease severity
All presented at: SLEEP 2019; June 8-12, San Antonio.
Also:
American Academy of Sleep Medicine Fact Sheet on Obstructive Sleep Apnea. https://aasm.org/resources/factsheets/insomnia.pdf. Accessed July 1, 2019.
Disclosures: Healio Primary Care was unable to determine the researchers’ relevant financial disclosures prior to publication.
Perspective
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This drug provides substantial benefits to hastening sleep onset and promoting sleep maintenance in those with insomnia with a treatment effect that persists for months. Lemborexant dampens wakefulness and is one of only two medications that influence the orexin system in the brain. The drug provides another important option for treating both sleep onset and sleep maintenance insomnia, giving doctors a powerful medication to help these patients fall asleep and stay asleep night after night.
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