Eisai scores an FDA approval for a homegrown sleep drug

Eisai’s bet on a better insomnia drug, whose symptoms affect up to a third of all adults, has been rewarded by the FDA with an approval. But with safety being a big issue for sleep drugs, the new therapy faces an uphill climb to gain acceptance with doctors and patients.

Just earlier this year, the FDA imposed black box warnings on a clutch of insomnia drugs, such as Lunesta, Sonata, and Ambien, due to reports of dangerous activity such as sleepwalking and sleep-driving that have led to injuries and deaths.

The new Eisai drug Dayvigo (known chemically as lemborexant)was developed in-house by the Japanese drugmaker. It works by inhibiting orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptors 1 and 2). Orexins are chemicals involved in sleep and arousal naturally produced by the hypothalamus.

“There’s still unmet need (within insomnia) as it relates to both efficacy and safety,” Tushar Patel, Eisai’s global lead for sleep-wake disorders in the neurology business group, noted in an interview with Endpoints News. “And we think in Dayvigo we have a product that addresses both (sleep) onset and maintenance, and does that in a way without impairing postural stability and cognition in the morning.”

Dayvigo was tested in two late-stage trials, with safety data over a 12 month period. Unlike many older insomnia drugs, the Eisai drug was not associated with rebound insomnia following treatment discontinuation. It was also tested in a trio of safety studies evaluating its impact on the ability to awaken to sound, next-day postural stability or memory, and next-morning driving impairment.

Although there were no major differences between Dayvigo and placebo on ability to awaken to sound, there was a dose-dependent worsening on measures of attention and memory for the drug versus placebo. In addition, there were no meaningful differences between the drug and placebo on next-day postural stability or memory or statistically significant impairment in next-morning driving performance.

Insomnia sufferers have a menu of options at their disposal. They can access over-the-counter antihistamines, benzodiazepines (such as Dalmane, Ativan), nonbenzodiazepine receptor agonists (such as Lunesta, Ambien), tricyclic antidepressants (such as Silenor), and melatonin agonists (such as Rozerem).

The most common pharmacological treatments are nonbenzodiazepine receptor agonists, or NonBzRAs, which are designed to cause sleepiness by enhancing GABA — a wide-reaching inhibitory neurotransmitter in the brain. But not all help patients maintain sleep through the night, and some have a plethora of unsavory side effects including sleepwalking, sleep eating, a heightened risk of falls and vehicular accidents.

The first medicine targeting orexin, Merck’s Belsomra, was approved in 2014. Since medicines focused on orexin — a neurotransmitter first discovered in 1998 — target a more localized area of the brain, the theory is that they will cause fewer side effects. However, Belsomra does carry a risk of impaired driving skills and can enhance the risk of falling asleep while driving.

There are other drugmakers developing orexin medicines for insomnia, including Idorsia and Minerva. So what makes Dayvigo special?

Ivan Cheung

“Those other compounds are in clinical development — they have shown something, and haven’t shown everything,” Ivan Cheung, chief of neurology of Eisai US, emphasized to Endpoints, referring to sleep onset, sleep maintenance, next morning safety measurements, efficacy over 6 months and safety over 12 months.

“Of course, I’m always about more treatment options for more patients,” he said. “All I can say is that it is not an easy task even if you think you have a great mechanistic drug to check all those boxes, and I think we’ve checked off a lot of boxes.”

Cheung did not offer any detail on the company’s pricing plans for the drug in insomnia.

Orexin signaling is implicated in other physiological functions such as memory, emotions, motivation, and attention. Therefore, Eisai is also testing the drug for use in Alzheimer’s disease, in addition to irregular sleep-wake rhythm disorder. The drug was previously being jointly developed with Purdue, but Eisai bought back all the rights to it earlier this year.

This content was originally published here.

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