FDA Approves Lemborexant (Dayvigo) for Insomnia Disorder—A Growing Problem

FDA Approves Lemborexant (Dayvigo) Approved for Insomnia Disorder—A Growing Problem

Dayvigo (lemborexant), developed and sponsored by Eisai, was approved by the Food and Drug Administration (FDA) for the treatment of insomnia characterized by difficulties with sleep onset or sleep maintenance in adult patients.  The approval of this new orexin receptor antagonist was based on the results of two Phase III studies called SUNRISE 1 and SUNRISE 2.

A Brief Overview of the Problem

According to some studies, 25% of the America’s adult population will experience insomnia at some point—other studies suggest about 15% to 20% of the adult population. Regardless of actual count, a lot of people struggle with sleep. Insomnia and sleep problems represent a tremendous problem. Worldwide, there may be up to 1.7 billion prevalent cases of insomnia; it is estimated that Asia has the largest number of prevalent cases at least back in 2016, according to some reports.

Many believe that with the advent of 24X7 real-time technology (internet, Smart Phones, social media, YouTube, etc.) that people cannot “turn off” and this wires the brain chemistry ever-ready for more stimuli. Hence, digital ubiquity impacts our sleeping patterns. Many articles and studies articulate this concern. The over use of and dependence on common sleeping pills, such as Ambien, unfortunately can lead to significant misuse and addiction

The Studies

In Neurology Advisor, Brian Park a Pharm D, noted that these approvals were based on SUNRISE 1 and SUNRISE 2—the both enrolling a total of 2,000 patients. As Park explained, in SUNRISE 1, the experimental drug (lemborexant) achieved its primary and secondary objectives—e.g. change from baseline in both sleep onset and sleep maintenance variables using objective polysomnography) vs. placebo and zolpidem tartrate extended-release (active comparator) in patients ≥55 with insomnia disorder.

In SUNRISE 2, lemborexant 5mg and 10mg resulted in a statistically significant improvement in subjective sleep onset latency vs. placebo (primary end point) as reported in sleep diaries. The doses of lembroexant led to statistically significant improvement in sleep maintenance variable of subjective sleep efficiency and subjective wake after sleep onset vs. placebo (key secondary end points).

In summary, lead investigator Dr. Russell Rosenberg and colleagues noted that based on the results of the “randomized clinical trial, lemborexant therapy significantly improved both sleep onset and sleep maintenance, including in the second half of the night, compared with both placebo and zolpidem measured objectively using polysomnography.” The experimental insomnia disorder drug was overall well tolerated, according to Rosenberg’s summary.

Additional Studies Probing for Safety

According to Eisai, the most common adverse reactions (reported in 5% or more of patients treated with Dayvigo and a least twice the rate of placebo) in SUNRISE 2 (the first 30 days) and SUNRISE 1 was somnolence. In fact, this newly approved drug may trigger this reaction more than the alternatives.

Additionally, Eisai conducted a number of studies to further evaluate the safety of the drug, including a study that assessed the effect of Dayvigo—these studies included: 1) Middle of the Night Study (108); 2) Effects of Next-day Postural Stability and Attention and Memory—(SUNRISE 1 and Study 108); 3) Middle of the Night (study 108) and 4) Effects on Driving (study 106).

The list of adverse events are included in the FDA label here

A Safer Alternative for Sleep?

One of the key principal investigators for Dayvigo, Russel Rosenberg, PhD, and colleagues recently wrote, “Lemborexant therapy significantly improved both sleep onset and sleep maintenance, including in the second half of the night, compared with both placebo and zolpidem.” They also noted the drug was generally well-tolerated, although Somnolence measurements were higher with lemborexant as noted previously.

According to a recent editorial accompanying the published study, lemborexant could be promising as a potentially safer and more effective alternative to the current popular insomnia medications. Michael A. Grandner, PhD, and Michael L. Perlis, PhD, noted that older insomnia medications can adversely affect cognition, memory and psychomotor behavior.

True Value of DAYVIGO

Only time will tell what the true value of this new approved medicinal product will be. It is a newer drug in what some may argue is a superior class with less risk for addiction and adverse events. How will it be priced? How will physicians and those studying sleep disorders evaluate it in use by patients?

Some commenters are cynicalDr. Josh Bloom of the American Council on Science and Health notes that lemborexant is second in a class that works via the dual orexin receptor antagonist mechanism.  The first such drug in this class was Belsomra from Merck, but according to Bloom’s reporting, the market is not fond of this product. Their “Report Card” ranks Dayvigo/lemborexant as working “a bit better than placebo” and “about the same as Ambien.” Belsomra produced $210 million in revenue in 2017 and $260 million in 2018TrialSite News cannot be certain that DAYVIGO is only “a bit better” than competitive alternatives. But what about pricing? This is where Bloom’s concern is apparent in that generic Ambien could be $2.90 per month as compared to Belsomera’s $353 per month. How will Eisai price Dayvigo?

Lead Research/Investigator

Russell Rosenberg, PhD, DABSM, was the principal investigator in the Dayvigo clinical trials and is a former Chairman of the Board of the National Sleep Foundation. Dr. Rosenberg is the Founder and Director of the Atlanta School of Sleep Medicine & Technology.