Forum Topics RMD RMD New competitor

Pinned straw:

Added 3 months ago

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)


PhilO
Added 3 months ago

Id like to see Resmed reducing the risk of a future Kodak moment and making some moves to become a one stop shop for sleep apnea treatment, putting some money into exploring alternative interventions and maybe even buying them. They’re the gorilla in this space and well positioned to do so.

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mikebrisy
Added 3 months ago

@Goitre The AD109 results for Phase III were reported in May of this year.

Mick Farrell, CEO $RMD, was questioned about them at the 4Q results in August. He downplayed AD109 as a competitive threat. He sees it as an incomplete therapy, overshadowed by GLP-1s, and unlikely to disrupt PAP’s role as the frontline standard of care. Instead, he framed it as part of the broader ecosystem of adjunct or fallback therapies where ResMed still intends to “own the relationship” with the patient.

In further detail:

Competitive Threat from Apnimed AD109

Farrell was asked directly about oral drugs for sleep apnea, specifically Apnimed’s positive Phase 3 result for AD109.

He described AD109 as a “third-tier” therapy, behind ResMed’s gold-standard PAP (CPAP, APAP, bilevel) and its silver-medal mandibular repositioning devices (dental).

He argued that GLP-1 drugs (e.g., Zepbound) are a stronger competitor than AD109. In his view, GLP-1s have “taken the wind out of the sails of Apnimed” because they not only reduce apnea-hypopnea index (AHI) by about 50%—similar to AD109—but also deliver cardiometabolic and weight-loss benefits that AD109 cannot match

Positioning of AD109

Farrell said AD109 and similar drugs “only half treat the apnea”, leaving significant residual disease.

He suggested they are more likely to be used in combination with gold-standard PAP therapy, not as standalone replacements

ResMed’s Strategy

ResMed intends to maintain relationships with patients regardless of therapy type—PAP, dental, drug, or implant.

Farrell emphasized that many patients who fail alternative therapies eventually return to PAP, quoting Professor Jean-Louis Pépin: “The best alternative to failing positive airway pressure therapy is positive airway pressure therapy again.”


My View

I have agonised as much as many on the implications of the competitive threats for CPAP, whether from GLP-1 or the AD109 class of compounds. Much has been written on this platform.

Clearly, Mick has a vested interest in downplaying the threat. But for the moment it appears that as long as the pharmaceutical treatments remain only partly effective, they are being prescribed in combination with CPAP (it is there in black and white in the treatment guidelines). I believe the real threat is not so much from AD109, but from potential future drugs, perhaps as yet undiscovered. Imagine a drug that reduce AHI by, say, 85% across 50%+ of the population. Now that would be problematic!

Additionally, and for now, $RMDs data indicates that the presence of pharmaceutical treatments is driving more patients into the treatment funnel, and $RMD gets to benefit from that.

There seem to be both tailwinds and headwinds at play here, and I don't think anyone can yet say with much confidence how this will play out over the next 3, 5 and 10 years.

To @PhilO 's point, I think it is indeed $RMD's goal to own the sleep quality / breathing quality space, using and building out from all their capabilities. I think they are unlikely to acquire a competitor with a drug that is only partly effective.

So, for now, I am just keeping a close eye on the quaterly sales volumes. While variable from period to period, there is no indication at the moment that we are seeing any decline. On the contrary, the growth in the latest period was one of the strongest for a while.

For sure it is one to keep an eye on, but for now I believe that $RMD can sustain double-digit earnings growth for the foreseeable future alongside the emerging pharamceutical therapies. It is important not to be complacent, but I will let the numbers continue to do the talking.

Disc: Held in RL only

30

Stumpy
Added 3 months ago

Medications which affect tissue tone will always have some form of side effect. When you have a mechanical ‘narrowing’ problem with the body, a mechanical option is often the most effective solution. Think stents to open blocked blood vessels or balloon sinuplasty for chronic sinus issues.

CPAP happens to be a viable mechanical option for sleep apnoea which can be self-applied by the patient with minimal risk. I would be more concerned for Resmed’s business if a new minimally-invasive, low-risk surgical intervention became available. Considering the location of the tissues that narrow in sleep apnoea, this is a serious challenge.

16

PhilO
Added 3 months ago

Fair enough. Medications are probably a step too far. A narrower focus on different self applied minimal risk interventions might be the sweet spot for their strategy. I just struggle to accept that the current device is as good as it gets into the future.

We’re pretty slow at identifying simple improvements sometimes. Like wheels on suitcases are relatively recent.

12

BoredSaint
Added 3 months ago

Its probably a bit too early to see the effects of this yet but there are some devices that are designed to be worn in childhood to help open up the airways which can help with prevention of OSA in adulthood. Obviously this is only targeting the subset of OSA patients who are affected due to the structure of their head and neck structures.

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