By Luigi Taranto Montemurro, MD, CSO of Apnimed and David P. White, MD, SVP Medical Affairs, Apnimed
It’s a familiar experience for many of us: a sleeping partner who snores, stops breathing or gasps for air. But we may not be familiar with these as potential signs of obstructive sleep apnea (OSA), a common and harmful sleep-related breathing disorder. Over 35 million people in the US and more than 900 million worldwide are thought to have OSA, and the majority of cases are undiagnosed.
In this article – the first in a series of three – we’ll discuss what OSA is, how it is currently treated and why we believe there is a pressing need for pharmaceutical treatment options. Finally, we’ll describe how recent research is helping companies like Apnimed in its efforts to address the challenges in developing potential treatment options.
What is OSA?
OSA is characterized by recurring periods during sleep when the upper airway collapses partially or completely, leading to reduced or absent breathing. The resulting disturbance to normal, restorative sleep and the associated oxygen levels going up and down often cause the patient to feel sleepy and fatigued during waking hours, adversely affect quality of life, and increase the risk of cardiovascular and metabolic diseases.
All patients with OSA share an anatomical disadvantage: a narrow upper airway in the oro-pharyngeal region that is prone to collapse during sleep. Various factors can result in this narrow airway, including fat deposits in the tissue surrounding the airway, increased tonsil or adenoid size, a long uvula (soft palate), and the specific shapes of the jaw and other facial bones.
However, not everyone with a narrow upper airway develops OSA. OSA also has a major neurobiological component involving the neural control of the genioglossus (tongue muscle), and roughly 20 other muscles in the upper airway that determine whether or not a narrow airway can or will collapse during sleep.
The complex anatomy and neurobiology of the upper airway, and the neurobiological changes that occur in the transitions from wakefulness to sleep states, has made understanding the pathophysiology of OSA, and the development of pharmaceutical treatment options, enormously challenging.
Devices vs. Drugs
Despite many efforts, so far there are no approved drug therapies that target the underlying causes of OSA; the main treatments utilize medical devices. The most widely prescribed treatment is continuous positive airway pressure (CPAP), which came into use in the 1980s. CPAP keeps the upper airway open during sleep by delivering pressurized air through a mask.
Other less prescribed treatments include oral appliances that mechanically push the jaw forward to enlarge the pharyngeal airway (mandibular advancing devices) and surgery that removes soft tissues from the pharynx to enlarge the airway.
The latest therapy to come along for OSA is hypoglossal nerve stimulation, which uses a surgically implanted electrical device that opens the airway by stimulating the nerve that innervates the genioglossus, a major upper airway dilator. FDA approved the first hypoglossal neurostimulator in 2014.
However, these therapies may not present every patient with an option they find feasible. For example, some studies have described fairly low rates of CPAP compliance, with 8-15% of patients discontinuing CPAP after one night and at least 50% discontinuing it within a year.1,2,3 Hypoglossal neurostimulators require a surgical procedure that some patients may find unappealing, and only a minority of OSA patients qualify for the therapy. Consequently, the clinical community continues to search for new treatment options to help manage OSA in their patients.
There is hope on that front. Over the last 10-15 years, researchers have begun to unravel the complex neurobiology of upper airway muscle control during sleep and how it contributes to OSA. Armed with that understanding, researchers have identified potential drug targets for treating the condition.
In our next two articles, we’ll take a close look at these advances in OSA and discuss how Apnimed is harnessing the latest research in its efforts to develop pharmaceutical treatment options for OSA and other related sleep disorders.
FOR ADDITIONAL INFORMATION:
 Borker PV, et al. Am J Respir Crit Care Med. 2021;204(3):339-346. doi:10.1164/rccm.202009-3685OC.
 Contal O, et al. Front Med (Lausanne). 2021;8:626361. doi:10.3389/fmed.2021.626361.
 Rotenberg BW, et al. J Otolaryngol Head Neck Surg. 2016;45(1):43. doi:10.1186/s40463-016-0156-0.