Unmet Medical Need: Excretion

1. Disease Summary:

2. Global Prevalence and Disease Burden:

• Overactive Bladder (OAB): Affects approximately 12-17% of adults globally, with higher prevalence in older populations. It is associated with significant healthcare costs due to frequent doctor visits, medications, and potential surgical interventions (PMID: 26671329).
• Constipation: Affects about 16% of the global population, with higher rates in women and older adults. It can lead to complications such as hemorrhoids and fecal impaction, increasing healthcare costs (PMID: 19549122).
• Hyperkalemia: Affects around 1-10% of hospitalized patients, particularly those with chronic kidney disease or those on certain medications. It poses a risk of severe cardiac complications, leading to increased morbidity and mortality (PMID: 25047526).
• Hyperammonemia: While exact prevalence is difficult to determine, it is commonly associated with liver disease and can lead to neurological complications. The economic burden includes hospitalizations and long-term care costs (PMID: 32491436).

3. Unmet Medical Need:

• Overactive Bladder (OAB): Many patients experience inadequate symptom relief from current treatments, such as antimuscarinic agents, due to side effects like dry mouth and constipation, leading to poor adherence (PMID: 26671329). There is a need for more effective therapies with better tolerability profiles.
• Constipation: Current treatments, including laxatives, often fail to provide adequate relief for chronic constipation. Patients may experience side effects or develop tolerance, necessitating new therapeutic options that target underlying mechanisms (PMID: 19549122).
• Hyperkalemia: Current management strategies often involve dietary restrictions and medications that may not be effective for all patients. There is a need for novel therapies that can effectively lower potassium levels without adverse effects (PMID: 25047526).
• Hyperammonemia: Treatment options are limited, primarily focusing on dietary management and lactulose. There is a need for innovative therapies that can more effectively reduce ammonia levels and prevent neurological damage (PMID: 32491436).

4. Current Treatment Options:

• Overactive Bladder (OAB):
  • Antimuscarinic agents (e.g., oxybutynin, tolterodine) are first-line treatments but have low adherence due to side effects.
  • Beta-3 adrenergic agonists (e.g., mirabegron) offer an alternative but may not be effective for all patients (PMID: 26671329).
• Constipation:
  • Laxatives (e.g., polyethylene glycol, bisacodyl) are commonly used but may lead to dependency and tolerance (PMID: 19549122).
  • Prokinetic agents and fiber supplements are also available but may not address all underlying causes.
• Hyperkalemia:
  • Diuretics and potassium binders (e.g., sodium polystyrene sulfonate) are used, but they may not be effective in all patients and can have side effects (PMID: 25047526).
• Hyperammonemia:
  • Lactulose is the standard treatment, but it may not be effective in all cases and can cause gastrointestinal discomfort (PMID: 32491436).

5. Current Clinical Trials:

• Trials investigating new pharmacological agents for OAB, including novel beta-3 agonists and combination therapies.
• Studies exploring the efficacy of new laxatives and prokinetic agents for chronic constipation.
• Research on innovative treatments for hyperkalemia, including new potassium binders and renal protective agents.
• Trials focused on novel therapies for hyperammonemia, including ammonia scavengers and enzyme replacement therapies.

6. Additional Context: