Wondering if anyone else has heard about the positive trial results from a new competitor: US-based biotech company Apnimed which announced successful Phase 3 results for its oral drug AD109. It targets obstructive sleep apnea (OSA) pharmacologically, potentially providing a simpler alternative to ResMed’s CPAP devices.

AD109: A Breakthrough Oral Treatment for Obstructive Sleep Apnea

AD109 is a first-in-class oral medication showing exceptional promise for treating obstructive sleep apnea (OSA), with consistent Phase 3 trial results demonstrating significant efficacy across diverse patient populations.

Clinical Trial Results and Effectiveness

Phase 3 Trial Outcomes:

• SynAIRgy trial: 55.6% reduction in AHI (Apnea-Hypopnea Index) from baseline at 26 weeks compared to placebo (p=0.001)
• LunAIRo trial: 46.8% reduction in AHI from baseline at 26 weeks vs. 6.8% with placebo (p<0.001)
• Both trials enrolled over 600 participants each, representing mild, moderate, and severe OSA across all weight classes

Key Efficacy Measures:

• Complete disease control: 22-23% of patients achieved AHI <5 events/hour
• ≥50% AHI reduction: Achieved by approximately 51% of participants
• Disease severity improvement: 45-51% of participants moved to a lower OSA severity category
• Oxygenation improvements: Significant reductions in hypoxic burden and oxygen desaturation index

Mechanism of Action

AD109 combines two active ingredients that work synergistically to address the root cause of OSA:

Aroxybutynin (2.5mg): A novel antimuscarinic agent that blocks certain receptors in the upper airway muscles

Atomoxetine (75mg): A selective norepinephrine reuptake inhibitor that increases norepinephrine levels in the brainstem

Combined Effect: The drug targets the hypoglossal motor nucleus to increase signals to upper airway muscles during sleep, preventing airway collapse without requiring external devices like CPAP machines. This approach increases genioglossus muscle responsiveness by approximately threefold compared to placebo.

Safety Profile

AD109 has demonstrated a favourable safety profile across multiple clinical trials: https://pmc.ncbi.nlm.nih.gov/articles/PMC10765395/

Common Side Effects (mild to moderate):

• Dry mouth
• Insomnia
• Urinary hesitancy
• Mild increases in heart rate (8-9 beats/minute)

Safety Highlights:

• No serious adverse events related to AD109 reported in Phase 3 trials
• Well-tolerated across diverse patient populations
• Side effects consistent with known profiles of individual drug components
• No clinically relevant changes in blood pressure, prostate function, or cognitive measures

Market Impact and Timeline

Regulatory Timeline: Apnimed plans to submit a New Drug Application (NDA) to the FDA by early 2026, with AD109 having received Fast Track Designation in 2022

Market Significance: If approved, AD109 would be the first oral pharmacotherapy for the estimated 80+ million Americans with OSA, potentially addressing the large population of patients who cannot tolerate or refuse CPAP therapy.

The consistent results across two large Phase 3 trials, combined with the novel mechanism targeting the neuromuscular root cause of OSA, position AD109 as a potentially transformative treatment option that could reshape the sleep apnea treatment landscape.

AD109 vs CPAP Comparison

AD109 Performance:

• AHI reduction: 46.8-55.6% reduction from baseline
• Complete disease control: 22-23% of patients achieve AHI <5 events/hour
• ≥50% AHI reduction: Achieved by ~51% of participants

CPAP Superiority:

• Greater efficacy: CPAP demonstrates 73-86% AHI reduction vs AD109's 46-56%
• More complete control: CPAP achieves AHI <5 in most compliant patients vs 22-23% with AD109
• Consistent performance: CPAP effectiveness is not dependent on drug metabolism or individual response variability

Clinical Significance

CPAP Advantages:

• Immediate and reversible effect - works every night it's used
• Near-complete elimination of events during proper use
• Proven long-term cardiovascular and health benefits
• Adjustable pressure settings for individual optimization

AD109 Considerations:

• Offers convenience as an oral medication without equipment
• May benefit patients who cannot tolerate CPAP therapy
• Represents meaningful improvement for mild-moderate OSA where CPAP compliance is poor
• Still leaves majority of patients with residual sleep apnea (AHI >5)