Pipeline Insight: Antidyslipidemics - The Power of Two

TABLE OF CONTENTS

ABOUT DATAMONITOR HEALTHCARE

• About the cardiovascular pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

• Datamonitor insight into the antidyslipidemics market
• R&D pipeline dynamics
• Guideline recommendations for an aggressive treatment approach emphasizes a need for more treatment options
• Pfizers atorvastatin + torcetrapib combination to become a blockbuster drug
• JTT-705- the most promising adjunct in development

CHAPTER 2 PIPELINE OVERVIEW & FUTURE FOCUS

• Pipeline overview
• PPAR agonists dominate the antidyslipidemic pipeline
• Greatest number of drugs in Phase II of development
• Pfizer has the greatest number of products in development
• Heavy investment from Japanese-based pharmaceutical companies
• Pfizers strategy to success
• Pfizer protecting its revenue
• Pfizers strategy under scrutiny
• Thought needs to be given to pricing strategy
• Merck - the loss of Zocors patent
• Diversifying its portfolio
• In-licensing
• Expansion
• Streamlining
• HeartPro and Vytorin

CHAPTER 3 PIPELINE DYNAMICS

• Definition of dyslipidemia
• What is dyslipidemia?
• Segmentation of dyslipidemia
• Markers for dyslipidemia
• Main types of dyslipidemia
• Hypercholesterolemia
• Familial hypercholesterolemia
• Hypertriglyceridemia
• Familial hypertriglyceridemia
• Mixed dyslipidemia
• Epidemiology of dyslipidemia
• The greatest unmet need in dyslipidemia according to key opinion leaders, is for drugs with the ability to prevent or reverse atherosclerosis
• Drugs need to prevent or even reverse the progression of atherosclerosis
• Drugs with novel mechanisms of action
• Drugs with increased efficacy in lowering LDL and increasing HDL
• More long-term data is required to support primary and secondary prevention of acute CVD events.
• More combination therapies are needed
• Additional statin safety studies not required

CHAPTER 4 R&D APPROACH

• Classification of pipeline products
• Statins and statin combinations
• Statins dominate the antidyslipidemic market
• Mechanism of action
• Atorvastatin + CETP inhibitor
• Simvastatin + niacin
• Fibrates - PPAR alpha agonists
• Fibrate + biguanide
• Other non-statin therapies
• Acyl-CoA cholesterol acetyltransferase (ACAT) inhibitors
• Ileal bile acid transport (IBAT) inhibitors
• Lipoprotein lipase activator
• Microsomal triglyceride transfer (MTP) inhibitors
• Squalene synthetase inhibitor
• Bile acid reabsorption inhibitor
• Adenosine A1A receptor agonist
• Apolipoprotein B100 antagonist
• Dual PPAR agonists
• PPAR delta agonist
• VCAM inhibitor
• Hypolipemic agent
• Lipoprotein regulator
• Transcription factor inhibitor
• Cholesterol absorption inhibitors
• Clinical trial design in dyslipidemia
• Short term endpoints: controlling cholesterol levels
• Long term endpoints: reduction in morbidity and mortality

CHAPTER 5 SINGLE-PILL STATIN COMBINATION LATE-STAGE DRUG ANALYSIS & FORECASTS

• Overview for single-pill statin combination drugs 
• Pipeline summary
• Definition of current comparator therapy
• Pfizers Lipitor remains the current comparator therapy
• Lipitors rise to prominence
• KS-01-019
• Clinical trials still underway
• Good patient potential
• Marketing of Advicor provides Kos with experience
• KS-01-019 performance will depend on its long-term data
• SWOT analysis
• Forecast to 2015
• Atorvastatin + torcetrapib
• Extensive Phase III trial underway
• Significant increases in HDL cholesterol seen in Phase II trials
• Elevations of 16-91% in HDL are seen in Phase I trials
• Good patient potential if it can prove to reduce the progression of CHD
• Marketing strategy aims to help Pfizer retain monopoly
• The overall performance of atorvastatin + torcetrapib combination is lower than atorvastatin
• SWOT analysis
• Forecast to 2015
• Datamonitor drug assessment summary

CHAPTER 6 FIBRATES AND FIBRATE COMBINATIONS LATE-STAGE DRUG ANALYSIS AND FORECASTS

• Pipeline summary
• Fenofibrate is the current comparator therapy
• Fenofibrate + metformin single-pill combination
• No clinical trial data
• Limited patient potential
• Previous experience in marketing fenofibrate and metformin should enable Merck and Fournier to market the drug successfully
• Overall performance rated lower than fenofibrates
• SWOT analysis
• Forecast to 2015
• LCP Feno
• LCP Feno met both primary and secondary objectives in clinical trial
• LCP Feno offers another choice of fibrate for physicians
• Marketing partner for LCP Feno is unknown
• LCP Fenos performance rated lower than fenofibrate
• SWOT analysis
• Forecast to 2015
• Datamonitor drug assessment summary

CHAPTER 7 ADJUNCTIVE THERAPY LATE STAGE ANALYSIS

• Pipeline summary
• Three different comparator therapies
• Implitapide
• Phase II trials are ongoing
• Phase I showed significant lowering of LDL of up to 58%
• Potential alternative to statins
• Co-marketing deal may boost sales
• Implitapides performance rated lower than atorvastatin
• Forecasts to 2015
• JTT-705
• 34% increase in HDL in Phase II clinical trials
• Excellent patient potential as adjunctive therapy
• Marketing factors
• JTT-705 shows better potential than Niaspan
• Forecast to 2015
• Pamaqueside
• Phase I trial showed a 12% reduction in LDL cholesterol
• Further trials required to determine patient potential
• Pamaqueside will benefit from Pfizers marketing experience
• Pamaqueside assessed performance lower than Zetia
• Forecast to 2015
• Gemcabene
• Clinical trial data shows significant increases in HDL
• Gemcabene needs to prove itself as an adjunct to perform well in the market
• Gemcabene has Pfizers marketing strength behind it
• The unavailability of long-term data lowers overall performance to poorer than fenofibrate
• Forecasts to 2015
• FM VP4
• Phase I trials show excellent safety profile
• Phase II trials still underway
• Potential as a safe top-up drug
• FM VP4 will require a marketing partner
• Overall performance rated less than Zetia
• Forecast to 2015
• Datamonitor drug assessment summary

CHAPTER 8 COMPARATIVE FORECASTS

• Comparative analysis

CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS

• Gene therapy appears to be a key therapy in preclinical development for dyslipidemia

APPENDIX A

• Epidemiology methodology
• Datamonitor forecast methodology
• Methodology
• US
• Japan
• France
• Germany
• Italy
• Spain
• UK
• Datamonitor drug assessment summary
• Contributing experts
• Bibliography
• Epidemiology sources
• US
• Japan
• France
• Germany
• Italy
• Spain
• UK
• Clinical trial data
• Report methodology
• About Datamonitor
• About Datamonitor Healthcare
• Datamonitor Healthcares therapy area capabilities
• About the cardiovascular analysis team
• Disclaimer
• List of Tables
• Table 1: R&D pipeline in the antidyslipidemic market, 2005
• Table 2: Antidyslipidemic pipeline, 2005
• Table 3: Phase of development of products in each class, 2005
• Table 4: Composition of the antidyslipidemic R&D pipeline by company.
• Table 5: Key changes to lipid levels between the NCEP II and NCEP III
• Table 6: Epidemiology overview of dyslipidemia, 2005-15
• Table 7: Epidemiology figures by age for the seven major markets, 2005
• Table 8: Total epidemiology figures by age for the seven major markets, 2005
• Table 9: R&D pipeline in the antidyslipidemic market, 2005
• Table 10: Key products in late-stage R&D pipeline for single pill statin combination drugs, 2005
• Table 11: Global sales of the leading branded statins, 2003-04
• Table 12: Lipitor: key facts
• Table 13: Factors affecting the revenues of simvastatin + Niaspan, 2007-15
• Table 14: Phase II trial results of atorvastatin + torcetrapib combination
• Table 15: Factors affecting the revenues of atorvastatin +torcetrapib, 2008-15
• Table 16: Research, clinical and commercial attractiveness summary for pipeline single-pill statin combination drugs
• Table 17: Key products in late-stage R&D pipeline for HDL targeting agents & combinations, 2005
• Table 18: Lipanthyl/Tricor: key facts
• Table 19: Factors affecting the revenues of metformin + fenofibrate, 2007-15
• Table 20: Factors affecting the revenues of LCP Feno, 2010-15
• Table 21: Research, clinical and commercial attractiveness summary for pipeline fibtates and fibrate combination drugs
• Table 22: Key products in late-stage R&D pipeline for HDL targeting agents & combinations, 2005
• Table 23: Niaspan: key facts
• Table 24: Zetia: key facts
• Table 25: Factors affecting the revenues of implitapide, 2009-15
• Table 26: Factors affecting the revenues of JTT-705, 2009-15
• Table 27: Factors affecting the revenues of pamaqueside, 2009-15
• Table 28: Factors affecting the revenues of gemcabene, 2009-15
• Table 29: Factors affecting the revenues of FM VP4, 2008-15
• Table 30: Research, clinical and commercial attractiveness summary for pipeline adjunctive therapies
• Table 31: Global sales forecasts for anti-dyslipidemic drugs, 2005-15
• Table 32: Drugs in preclinical development for dyslipidemia, 2005
• Table 33: Datamonitor drug assessment parameters
• List of Figures
• Figure 1: Pipeline overview of antidyslipidemic drugs
• Figure 2: Percentage of R&D products in each phase of development, 2005
• Figure 3: Composition of the antidyslipidemic R&D pipeline by country, 2005
• Figure 4: Composition of the antidyslipidemic R&D pipeline by company type
• Figure 5: Unmet needs in the dyslipidemia market, 2005
• Figure 6: Assessment of KS-01-019s performance indicators
• Figure 7: KS-01-019 SWOT analysis
• Figure 8: Global sales forecasts for simvastatin + Niaspan, 2007-15
• Figure 9: Assessment of atorvastatin + torcetrapibs performance indicators
• Figure 10: SWOT analysis of atorvastatin + torcetrapib combination
• Figure 11: Global sales forecasts for atorvastatin + torceptrapib, 2008-15
• Figure 12: Research/clinical and commercial attractiveness of single-pill statin combinations
• Figure 13: Datamonitors drug assessment summary for the late-phase pipeline single-pill statin combination drugs
• Figure 14: Assessment of metformin + fenofibrate performance indicators
• Figure 15: Metformin + fenofibrate SWOT analysis
• Figure 16: Global sales forecasts for metformin + fenofibrate, 2007-15
• Figure 17: Assessment of LCP Fenos performance indicators
• Figure 18: LCP Feno SWOT analysis
• Figure 19: Global sales forecasts for LCP Feno, 2006-15
• Figure 20: Research/clinical and commercial attractiveness of fibrate and fibrate combination drugs
• Figure 21: Datamonitors drug assessment summary for the late-phase pipeline single-pill statin combination drugs
• Figure 22: Assessment of implitapides performance indicators
• Figure 23: Global sales forecasts for implitapide, 2009-15
• Figure 24: Assessment of JTT-705s performance indicators
• Figure 25: Global sales forecasts for JTT-705, 2009-15
• Figure 26: Assessment of pamaquesides performance indicators
• Figure 27: Global sales forecasts for pamaqueside, 2009-15
• Figure 28: Assessment of Gemcabenes performance indicators
• Figure 29: Global sales forecasts for Gemcabene, 2009-15
• Figure 30: Assessment of FM VP4s performance indicators
• Figure 31: Global sales forecasts for FM VP4, 2008-15
• Figure 32: Research/clinical and commercial attractiveness of adjunctive therapies
• Figure 33: Datamonitors drug assessment summary for the late-phase pipeline adjunctive therapies
• Figure 34: Datamonitors drug assessment summary for the late-phase antidyslipidemic pipeline drugs
• Figure 35: Example of Datamonitor drug assessment scorecard
• Figure 36: Example of Datamonitor drug assessment graph