Sleep is so important—that’s why the biopharma industry is addressing the gaps in available insomnia therapies. Learn about sleep struggles, future research and treatments, and “Coronasomnia” below.
Struggling to Sleep
The World Sleep Society has identified three elements associated with high-quality sleep: duration, continuity, and depth. Sleep length should be long enough to sufficiently rest the sleeper, allowing them to be alert the following day. Sleep periods should be seamless and unfragmented, and sleep should be deep enough to be restorative. These principles seem easy enough to achieve, but more than 100 million Americans across all age groups aren’t sleeping well.
Experts recommend that adults should sleep for somewhere between seven and nine hours per night. However, nearly 30% of adults get fewer than six hours of sleep per night, and only 30% of high school students report at least eight hours of sleep on an average school night. Data from the National Sleep Foundation’s Sleep In America polls over the last several years has also uncovered alarming sleep trends, from increased daytime sleepiness to poor sleep scheduling, to an inability among American adults to prioritize getting a good night’s rest.
On top of the socioeconomic drivers of poor sleep, over 80 types of sleep disorders can affect a person’s sleep. Roughly 70 million people in the United States have a sleep disorder, including the four most common sleep conditions: insomnia, sleep apnea, restless leg syndrome, and narcolepsy. Regardless of the cause, consistent poor sleep can cause fatigue, decreased energy, irritability, and problems focusing, as well as an inability to make decisions and poor effects on mood, causing or exacerbating depression and anxiety. Chronic health problems like heart disease and diabetes have also been linked to poor sleep.
Insomnia is the most common sleep disorder. Most diagnoses fall into two categories: sleep-onset insomnia, or difficulty falling asleep, and sleep maintenance insomnia, or difficulty staying asleep after falling asleep initially. Mixed insomnia, which combines both insomnia categories, can also be experienced, particularly among people with chronic insomnia whose symptoms shift over time.
Insomnia isn’t only a long-term chronic condition; between 30% and 35% of adults have experienced brief symptoms of insomnia, and 15% to 20% of adults have experienced short-term insomnia, which lasts for fewer than three months. Insomnia affects one in four women, who are more likely overall to have insomnia compared with men due to hormonal changes that can induce insomnia episodes.
The good news? Because insomnia is so common, it represents a considerable market of interest for biopharmaceutical companies and drug developers. Hundreds of clinical trials are currently underway, and the sales market for insomnia treatments is projected to grow over the next few years.
“PRA Health Sciences has participated in numerous sleep disorder studies and is an industry leader in sleep medicine studies,”says Ameet Daftary, MD, MS, MBA, Medical Director, Pediatrics/Pulmonology & Sleep Medicine, and board certified sleep medicine specialist. “Sleep is crucial to quality of life and personal well-being. As we continue to learn more about the biologic processes that regulate sleep and discover new molecular targets, we look forward to overseeing even more studies that will ultimately improve patients’ lives.”
Current treatment guidelines vary, and several sleep groups have published guidelines for insomnia management, including the American College of Physicians in 2016, the American Academy of Sleep Medicine in 2017, the Agency for Healthcare Research and Quality in 2017, and the British Association for Psychopharmacology in 2019. The current treatment paradigm includes symptom evaluation, initiation of cognitive behavioral therapy (CBT), the addition of nonpharmacologic treatments, and if no improvement is seen, a combination of CBT with evidence-based pharmacology.
The American Academy of Sleep Medicine supports complementary use of pharmacologic agents for the treatment of insomnia. They recommend a number of medications, including suvorexant, eszopiclone, zolpidem, triazolam, and temazepam for sleep maintenance or sleep-onset insomnia. Most approved insomnia therapies, excluding doxepin and ramelteon, are Schedule IV controlled substances with a low but noted potential for abuse.
The goals for insomnia treatment are to improve quality of sleep and poor daytime functioning, as well as to reduce the distress and anxiety that people experience with sleep fragmentation. Withdrawal from CBT treatment for insomnia is high—estimated at 40% before the treatment midpoint—and over-the-counter treatments are not recommended due to a lack of safety and efficacy data. The gap in these strategies is obvious and can be filled by the development of a safe and effective pharmacologic therapy.
Currently, available medications that target the receptors that contribute to sleep-wake cycle regulation include γ-aminobutyric acid (GABA-A), melatonin, histamine, and orexin/hypocretin receptors. GABA-A agonists, benzodiazepines, nonbenzodiazepine GABA-A agonists (also known as “Z-drugs”), sedating antidepressants, and melatonin receptor agonists are all potential pharmacologic treatments. As with any medication therapy, though, risks and potential side effects are present, varying from abuse and dependency, daytime drowsiness, increased fall and fracture risk, and delirium.
Future Insomnia Treatments
Orexin receptor antagonists are the latest target for pharmacologic development. Orexin was first discovered in 1998 by two independent research groups conducting animal model studies. Since then, researchers have delved deeper into the potential role of orexins—neurotransmitters that regulate sleep and wakefulness—in treating insomnia.
The first orexin receptor antagonist was approved by the United States Food and Drug Administration (FDA) in August 2014. Suvorexant blocks both the orexin-1 and orexin-2 receptors, suppressing wakefulness. In multiple clinical trials, suvorexant was superior to a placebo in several subjective and polysomnography measured categories. Lemborexant was approved by the FDA in December 2019 and also treats sleep maintenance and sleep-onset insomnia. Lemborexant also improved numerous objective and subjective categories, with limited adverse events. Two other orexin receptor antagonists are currently in phase 3 clinical trials: nemorexant and seltorexant.
The industry is overall positive about the potential of the orexin receptor antagonist class of drugs. Compared with currently available treatments, the most common side effect associated with orexin therapy is drowsiness.
“Coronasomnia” Sweeping the Globe
COVID-19 has taken a toll on everyone’s health, up to and including sleep hygiene. Emerging research has identified COVID-related sleep disorders as a new category of sleep conditions. The combined pressures of quarantine, isolation, anxiety, stress, and financial loss have resulted in increases in insomnia, nightmares, fatigue, exhaustion, and changes in REM sleep behaviors.
“Coronasomnia”—the colloquial term for insomnia due to pandemic-related stress—has been identified as a new, significant problem in all age groups. Although much of the coronasomnia evidence is anecdotal, one study conducted early in the pandemic and published in early 2021 found high rates of clinically significant insomnia among both healthcare workers and the general population.
Regardless of the cause, good sleep is essential to good health, and poor sleep has been shown to be connected to physical health issues like obesity, diabetes, inflammation, poor functioning, and poor mental health. Until the root causes of poor sleep are addressed, and until adequate pharmaceutical treatments are available, World Sleep Day remains an important day to create global awareness.
World Sleep Day has been observed since 2008, hosted by the World Sleep Society. Each year, the event draws attention to important sleep-related issues, including education and sleep medicine, on the last Friday before the Spring Equinox. World Sleep Day will be observed this year on March 19, with the theme Regular Sleep, Healthy Future and with a goal of promoting advocacy and education initiatives that underline the importance of sleep as a means to achieve the best quality of life and improve global health.
Under the expert guidance of our in-house board-certified neurologists and psychiatrists, we have carried out pivotal trials leading to the approval of 20 drugs for the treatment, prevention, and cure of neurological, psychiatric, and pain disorders.
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