NeurologyLive® Top Stories of 2021: Sleep Medicine

The field of sleep medicine has experienced plenty of development in 2021, with much still ongoing following the COVID-19 pandemic and the introduction of telehealth for patient care. The team at NeurologyLive® has worked hard to keep our coverage up to date, including breaking news on FDA decisions, investigational treatments, and as ongoing research for multiple sleep disorders. 

From our conversations with sleep experts to our coverage of updated guidelines from the American Academy of Sleep Medicine (AASM), the sleep medicine space has progressed via FDA approvals and newly identified best practices for patients with insomnia, narcolepsy, obstructive sleep apnea, and other related conditions. 

We are looking back at our top stories in sleep medicine from this year, including our top-read stories discussing insomnia’s effect on complex daytime cognitive task performance, daridorexant’s efficacy in treatment insomnia, as well as the FDA’s approval of a new drug application for FT218 in narcolepsy. Browse the highlights below and learn more about ongoing discussions and expert conversations by visiting our Sleep Medicine clinical focus page.

Click the buttons below to learn more about each story.

1. Presence of Insomnia Shows Significant Effect on Complex Daytime Cognitive Task Performance

Results from a cross-sectional study published in August found that individuals’ level of daytime sleepiness impacts their ability to perform simple daytime cognitive tasks. In addition, presence of insomnia resulted in greater performance deficits on more complex tasks.¹

The study included 35 patients with insomnia and 54 normal sleepers, all of whom underwent 2 nights of home-based polysomnography followed by daytime testing with a 4-trial Multiple Sleep Latency Test. In responding to complex cognitive tasks, participants insomnia group had slower and more variable response latencies, produced fewer correct responses, and had more errors than normal sleepers.

Conversations on the effects of insomnia on individuals’ ability to function have been lonstanding in the field of sleep medicine, with many exploring new, nonpharmacologic approaches to addressing these challenges. Additional research has investigated the role of cognitive behavioral therapy (CBT-I) for insomnia, with several studies finding the treatment approach successful in patients, including older adults and postpartum women. In June 2021, the American Academy of Sleep Medicine presented recommendations developed by a task force of experts regarding the clinical practice use of behavioral and psychological treatment for chronic insomnia disorder in adults, strongly recommending CBT-I as a treatment approach.² 

2. Daridorexant Shows Efficacy as Insomnia Therapy With Evidence of No Withdrawal Effects

At the 2021 SLEEP Virtual Annual Meeting, June 10-13, poster presentations suggested that daridorexant, an investigational dual orexin receptor antagonist from Idorsia for the treatment of adult patients with insomnia, is effective in treating different aspects of the disorder. A total of 9 posters were presented at the meeting, which encompassed data from the Idorsia’s phase 3 clinical program evaluating daridorexant.³

Data from 1 poster presented at SLEEP 2021 suggest that any dose of the treatment, each more than placebo, increased total sleep time in a dose-dependent manner, lacking any impact on the proportion of all sleep stages in this patient population. Comparatively, another found that daridorexant improved objective sleep parameters for patients with mild to moderate obstructive sleep apnea, without modifying any sleep architecture, and a third presentation suggested that no withdrawal or rebound symptoms were associated with discontinuation of the treatment. 

The NDA for the daridorexant was originally accepted by the FDA for review a few months earlier in March 2021, including data from a comprehensive clinical and nonclinical development program demonstrating that the treatment maintained a favorable safety profile while also showing the efficacy in subjective sleep parameters and improvement in daytime functioning. Daridorexant was the first sleep medication to demonstrate these improvements in sleep and daytime functioning, measured by a newly developed and validated instrument. If approved, daridorexant is anticipated to be launched in the US in the first half of 2022.⁴ 

3. FDA Accepts NDA for FT218 in Treatment of Narcolepsy Symptoms

In March 2021, the FDA announced that it had accepted an NDA from Avadel Pharmaceuticals for its investigational agent, FT218, in the treatment of excessive daytime sleepiness and cataplexy in adults with narcolepsy. The NDA for the once-nightly sodium oxybate formulation was supported by data from the phase 3 REST-ON study (NCT0270744), which was conducted under a special protocol agreement with the FDA and met all 3 of its co-primary end points in change on Maintenance of Wakefulness Test scores, Clinical Global Impression-Improvement scores, and mean weekly cataplexy attacks.⁵ 

Additional data from the completed REST-ON trial were presented later in the year at the 2021 American College of Chest Physicians (CHEST) virtual meeting, October 17-20. Post hoc data included analyses of sleep latency response and cataplexy response with once-nightly use of the formula, as well as findings from a discrete choice experiment evaluating patients’ treatment preferences. 

Although FT218 was originally given a Prescription Drug Use Fee Act (PDUFA) action date of October 15, 2021, the FDA announced that the application was still under review at that time. To date, the FDA has not announced a new PDUFA action date for FT218. “We have addressed all questions received to date and remain confident that the package we have submitted satisfies all of the FDA’s requests. We have not been informed of any deficiencies in our application and remain fully committed to work closely with the FDA for the duration of its review of our NDA for FT218,” Greg Divis, CEO, Avadel, said in a statement announcing the ongoing review.⁶ “Once-at-bedtime FT218 has the potential to truly impact the way people with narcolepsy are able to live their lives and we are dedicated to making this important therapy available to patients as quickly as possible.”

REFERENCES
1. Edinger J, Bathgate CJ, Tsai S, Khassawneh B. Impact of daytime sleepiness and insomnia on simple and complex cognitive task performances. Sleep Med. 2021;87:46-55 doi:10.1016/j.sleep.2021.08.004
2. Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and Psychological Treatments for Chronic Insomnia Disorder in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Presented at SLEEP 2021 Annual Meeting; Virtual; June 10-13. Abstract LBA001.
3. Idorsia to present new Phase 3 data on daridorexant in insomnia at SLEEP 2021. News release. Idorsia. June 9, 2021. Accessed December 21, 2021. https://www.globenewswire.com/news-release/2021/06/09/2244070/0/en/Idorsia-to-present-new-Phase-3-data-on-daridorexant-in-insomnia-at-SLEEP-2021.html
4. FDA Accepts the new drug application for review of Idorsia’s daridorexant for the treatment of adult patients with insomnia. News release. Idorsia. March 10, 2021. Accessed December 21, 2021. http://www.globenewswire.com/news-release/2021/03/10/2190042/0/en/FDA-accepts-the-new-drug-application-for-review-of-Idorsia-s-daridorexant-for-the-treatment-of-adult-patients-with-insomnia.html
5. Avadel Pharmaceuticals Announces FDA Acceptance of New Drug Application for FT218 in Adults with Narcolepsy for the Treatment of Excessive Daytime Sleepiness and Cataplexy. News release. March 1, 2021. Accessed March 2, 2021. https://www.globenewswire.com/news-release/2021/03/01/2184208/0/en/Avadel-Pharmaceuticals-Announces-FDA-Acceptance-of-New-Drug-Application-for-FT218-in-Adults-with-Narcolepsy-for-the-Treatment-of-Excessive-Daytime-Sleepiness-and-Cataplexy.html
6. Avadel Pharmaceuticals announces ongoing FDA review of NDA for FT218 for patients with narcolepsy. News release. Avadel Pharmaceuticals. October 15, 2021. Accessed October 15, 2021. https://www.globenewswire.com/news-release/2021/10/15/2315210/0/en/Avadel-Pharmaceuticals-Announces-Ongoing-FDA-Review-of-NDA-for-FT218-for-Patients-with-Narcolepsy.html