Abstract
Overview
Introduction
The increase in diabetic kidney disease is a worldwide problem. Current treatment centers on antihypertensives inhibitors for the renin-angiotensin system and merely retards the decline of renal function. A large unmet need thus exists for therapies that fully halt disease progression or provide curative benefit
Scope
- The prevalence and progression of diabetic nephropathy in the seven major markets is evaluated
- The foremost pharmacological strategies for the treatment of diabetic nephropathy are reviewed
- The current status of angiotensin II receptor blockade as first line therapy in the treatment of diabetic nephropathy is discussed
- An overview is given of the drugs in development for the treatment of diabetic nephropathy
Report Highlights
The necessity for aggressive blood pressure control is undisputed in the medical community, but the therapeutic focus is now extending to end-organ protection as a treatment goal of equal importance to BP reduction. Thus, commercial performance of both ACE inhibitors and ARBs is dependent on renoprotective benefits beyond blood pressure control
The pipeline for developmental drugs targeting the cause of diabetic kidney disease is dominated by endothelin receptor antagonists and advanced glycosylation end product inhibitors. The commercial potential for successful new agents is substantial as existing therapies do not halt the progression of diabetic nephropathy to end stage renal disease
Proximal blockade of the renin-angiotensin system (RAS) through renin inhibition offers greater treatment opportunities than distal inhibition via angiotensin II receptor blockade. Recent basic and clinical research supports the strong theoretical appeal of renin inhibition as the most promising pharmacological strategy in the short-to-medium term
Reasons to Purchase
- Explore the growing burden of ESRD on healthcare systems through data on the prevalence and progression of diabetic nephropathy
- Assess the potential of current treatment options in the diabetic nephropathy arena
- Identify novel R&D compounds in the diabetic nephropathy pipeline
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- About the cardiovascular pharmaceutical analysis team
- EXECUTIVE SUMMARY
- Introduction
- Scope and coverage of the Brief
- Methodology
- Key findings about the the topic
- EPIDEMIOLOGY
- Definition
- Etiology of diabetic nephropathy
- The role of hypertension in diabetic nephropathy
- Prevalence of hypertensive patients with diabetes
- Prevalence of hypertensive patients with diabetes
- Prevalence of nephropathy in type 2 diabetics
- Progression of diabetic nephropathy in type 2 patients.
- The growing burden of ESRD on healthcare systems
- Key factors influencing the ESRD market
- The increasing prevalence of ESRD
- ESRD occurrence is increasing in an aging population
- Increasing causal risk factors - diabetes andhypertension
- TREATMENT OF DIABETIC NEPHROPATHY
- Glucose control in diabetic nephropathy
- Importance of blood pressure control
- Pharmacological strategy: the role of therenin-angiotensin system
- The key components of the renin-angiotensin system
- The status of the renin-angiotensin system in diabetics
- Benefits of ACE inhibition
- Mechanism of action of ACE inhibitors
- Data supporting the renoprotective benefits of ACEinhibitors.
- The MICRO-HOPE study (2000): the benefits of ramipril
- The AASK study (2001): ramipril vs. metoprolol
- BENEDICT (2004): trandolapril
- DETAIL (2004): enalapril is not more efficacious thantelmisartan
- Benefits of angiotensin II receptor blockade
- Mechanism of action of angiotensin II receptor blockers
- Current status of angiotensin II receptor blocker use inpatients with diabetic nephropathy
- Overview
- The issue of dose in ARB-based therapy
- Class effect assumption
- FUTURE TREATMENT OF DIABETIC NEPHROPATHY
- Potential of the ACE/ARB combination
- Marketing rationale for the ACE/ARB combination
- Renin inhibition: what are the therapeuticopportunities?
- New compounds should target the underlying disease
- New approaches for diabetic microvascular complications
- Inhibitors of aldose reductase (ARIs)
- Protein kinase C-beta (PKC) inhibitors
- Advanced glycation end product (AGE) inhibitors
- Endothelin A receptor antagonists (ERAs)
- Potential treatments for diabetic nephropathy
- ALT-711
- ALT-946
- AVE-7688
- CR002
- Darusentan
- FG-3019
- KRX-101
- Pratosartan
- PTR-3173
- Pyridorin
- Ruboxistaurin (LY-333531)
- SPP-100 (aliskiren)
- SPP-301
- Conclusion
- Potential of the ACE/ARB combination
- APPENDIX
- Bibliography
- Epidemiology
- Treatment and novel agents
- Disclaimer
- Bibliography
- List of Tables
- Table 1: Changes in kidney structure and function indiabetic nephropathy
- Table 2: Prevalence of diabetic hypertension(millions), 2002-15
- Table 3: Diabetic hypertensive population bysub-population across the seven major markets (millions), 2002-15
- Table 4: Estimated prevalence of type 2 diabeticnephropathy in the seven major markets
- Table 5: Number of type 2 patients affected bydiabetic nephropathy and time of progression across the seven majormarkets (millions), 2003
- Table 6: Renal transplantation, hemodialysis andperitoneal dialysis prevalence rates by country (PMP), 2002
- Table 7: Hemodialysis population by country (in 000s),2002-12
- Table 8: The growth and distribution of the riskcausal factors in ESRD in the seven major nations
- Table 9: The growth and distribution of the riskcausal factors in ESRD in the seven major nations
- Table 10: Evolution of treatment guidelines withrespect to target blood pressure and therapy options: reducing the riskof nephropathy in patients with diabetes or kidney disease
- Table 11: JNC7: compelling indications for individualdrug classes
- Table 12: Pharmacokinetic profiles of commerciallyavailable ARBs
- Table 13: Current indications for ARBs in addition tohypertension
- Table 14: Dual RAS blockade in patients with diabeticnephropathy
- Table 15: Renin inhibition reduces plasma reninactivity
- Table 16: Nephropathy pipeline, 2005
- List of Figures
- Figure 1: Prevalence of diabetic hypertension, 2002-15
- Figure 2: Diabetic hypertensive population bysub-population across the seven major markets, 2002-15
- Figure 3: Estimated progression of diabeticnephropathy in type 2 diabetes across the seven major markets
- Figure 4: Increased risk of death and diabeticnephropathy
- Figure 5: Hemodialysis population by country, 2002-12
- Figure 6: Increasing prevalence of ESRD in thedeveloped world
- Figure 7: Hemodialysis is preferred over peritonealdialysis in all markets
- Figure 8: Age distribution and growth of prevalentESRD patients
- Figure 9: The increasing prevalence of diabetes andhypertension in the major seven nations
- Figure 10: Guideline-based treatment tree: use of ACEinhibitors and ARBs in nephropathy patients
- Figure 11: The renin angiotensin system
- Figure 12: Angiotensin II is a cardiovascular riskfactor with direct tissue effects
- Figure 13: Prorenin/renin receptor mediates the directtissue effects of renin and prorenin
- Figure 14: Pharmacological strategies for theinhibition of the renin-angiotensin system
- Figure 15: The AT2 receptor may have positive as wellas negative effects on the vasculature and end organs
- Figure 16: Mechanism of action of ACE inhibitors
