It is characterized by repetitive partial or complete upper airway obstructions that occur during sleep, resulting in intermittent hypoxemia, loud snoring, sleep disruption, and daytime sleepiness or fatigue. OSA is associated with metabolic and cardiovascular co-morbidities and possibly increased mortality and can impair work productivity, reduce functional ability, and lower quality of life. 

• Obstructive Sleep Apnea in Adults. Veasey SC et al. N Engl J Med. 2019 Apr 11;380(15):1442-1449.

• Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Benjafield AV et al. Lancet Respir Med. 2019 Aug;7(8):687-698.

Current treatment options are either cumbersome or uncomfortable to use yielding reduced adherence, or are unpredictable in their efficacy. In addition, most clinical metrics used today to define apnea severity have problems in their measurement and ability to predict adverse outcomes. 

• The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Azarbarzin A et al. Eur Heart J. 2019 Apr 7;40(14):1149-1157.

• The Sleep Apnea-Specific Hypoxic Burden Predicts Incident Heart Failure. Azarbazin A et al. CHEST 2020; 158(2):739-750.

• Hypoxic burden and heart-rate variability predict stroke incidence in sleep apnoea. Blanchard M et al. European Respiratory Journal, European Respiratory Society, 2021, 57 (3), pp.2004022.

• Metrics of Sleep Apnea Severity: Beyond the AHI. Malhotra A et al. Sleep, Volume 44, Issue 7, July 2021.

• Hypoxic Burden of sleep apnea: measurement and associations with outcomes . Azarbazin A. May 23, 2023.

• Online Hypoxic Burden Calculator based on an FDA-cleared automated sleep scoring tool (Somnolyzer 24×7, The Siesta Group) and on an algorithm published in Azarbarzin et al (2019). The calculator functions by analyzing uploaded polysomnographic recordings saved in .edf format.

AD109

Apnimed’s lead product candidate, AD109, represents a novel pharmacological approach that is specifically designed to target the neurological control and activation of upper airway dilator muscles to maintain an open airway during sleep. If approved, AD109 would be the first medication indicated to address the disordered nighttime breathing that characterizes obstructive sleep apnea. 

• Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA. Rosenberg R, Abaluck B, Thein S. J Clin Sleep Med. 2022;18(12):2837-2844.

• Development of a combination of noradrenergic and antimuscarinic drugs for the treatment of obstructive sleep apnea: Challenges and progress. Taranto-Montemurro L, Pho H and White DP. Front. Sleep 2:1148282.

• The Oral Agent AD109 Improves Objective and Subjective Outcomes in Obstructive Sleep Apnea Patients. Results From the MARIPOSA Study, a Randomized, Controlled Clinical Trial. Schweitzer P, Ojile JM, Thein S, Drake C, Rosenberg R, Corser B, Abaluck B, Sangal RB, Maynard J, MARIPOSA Trial Investigators. In: American Thoracic Society 2023 International Conference. Presented Sunday May 21, 2023, Washington, DC.

• The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial. Schweitzer PK, Taranto-Montemurro L, Ojile JM, Thein SG, Drake CL, Rosenberg R, Corser B, Abaluck B, Sangal RB; Maynard J. Epub before print.

AD504

Apnimed is developing AD504, a combination of atomoxetine with a proprietary formulation and trazodone designed for OSA patients with symptoms of disturbed sleep. 

• Effects of Atomoxetine plus a Hypnotic on Obstructive Sleep Apnea (OSA) Severity in Patients with a Moderately Collapsible Pharyngeal Airway. Corser B et al.

Supporting research for novel oral pharmaceuticals in OSA

Apnimed is the global leader in studying novel, oral pharmaceuticals as potential treatments for OSA. 

• The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. Taranto-Montemurro L et al. Am J Respir Crit Care Med Vol 199, Iss 10, pp 1267–1276, May 15, 2019.

• Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature. Taranto-Montemurro L et al. J. Clin. Med. 2019, 8, 1846.

• Effects of the Combination of Atomoxetine and Oxybutynin on OSA Endotypic Traits. Taranto-Montemurro L et al. Chest. 2020 Jun;157(6):1626-1636.

• A Randomized, Placebo-Controlled, Double-Blind Crossover Trial Assessing the Combination of Noradrenergic/Serotonergic Reuptake Inhibitor and an Antimuscarinic Agent for the Treatment of Obstructive Sleep Apnea. Thomson L et al. Am J Respir Crit Care Med 2020;201:A4521.

• Different antimuscarinics when combined with atomoxetine have differential effects on obstructive sleep apnea severity. Aishah A et al. J Appl Physiol 130: 1373–1382, 2021.

• Addition of zolpidem to combination therapy with atomoxetine+oxybutynin increases sleep efficiency and the respiratory arousal threshold in obstructive sleep apnoea: A randomized trial. Messineo L et al. Respirology. 2021;26:878–886

• Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options. Perger E and Taranto-Montemurro L. Curr Opin Pulm Med 2021 Nov 1;27(6):505-513.

• Reboxetine Plus Oxybutynin for OSA Treatment A 1-Week, Randomized, Placebo-Controlled, Double-Blind Crossover Trial. Perger E et al. CHEST 2022; 161(1):237-247.

• One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial, Aishah A et al. Ann Am Thorac Soc. 2022 Dec 20.

• Ato+Oxy for Symptomatic Snoring and Airflow Limitation, presented at ATS, 2022.

• Combination Pharmacological Therapy Targeting Multiple Mechanisms of Sleep Apnea, presented at ATS, 2022.

• Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility . Schweitzer PK et al. Sleep Breath (2022).

• The combination of atomoxetine and dronabinol for the treatment of obstructive sleep apnea: a dose escalating, open-label trial. Messineo L, Norman D, Ojile J. J Clin Sleep Med. 2023 Feb 21.

• Comparison of Night-to-Night and Inter-scorer Variability of Different Indices of Obstructive Sleep Apnea Severity in the MARIPOSA Trial. Pho H, Sands SA, Azarbarzin A, Wellman A, Messineo L, Strassberger C, Farkas R, White DP, Taranto-Montemurro L. In: American Thoracic Society 2023 International Conference. Presented Tuesday May 23, 2023, Washington, DC.