Table of Contents

Statin Adjunct Therapy - Zetia, Revenue Protection for Zocor? - Analysis of the role of adjunctive therapy in the treatment of dyslipidemia, focusing on the factors driving versus limiting the future uptake of Zetia (ezetimibe)

Product Code: BFHC0587

Publication Date: 26-May-2003

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Overview

Introduction

Statins are undisputedly the gold standard in the treatment of dyslipidemia and more efficacious monotherapies are unlikely to be identified and developed in the near future. However, an important unmet need lies in the effective control of patients with complicated lipid profiles. Therefore, agents that can be used as adjuncts to statin therapy are being increasingly prescribed.

Scope

· Assess the market potential for non-statin anti-dyslipidemics offering a novel mechanism of action or additional benefits to statin monotherapy

· Examine the potential of Zetia as an adjunct to statin therapy by assessing its benefits over existing adjunctive therapies

· Understand existing constraints which may limit the uptake of Zetia and potential threats to the long-term success of the drug

Report Highlights

With statins unable to adequately control cholesterol in all patients, there remains a strong need for novel therapies that enhance the benefits of statins. In turn, Zetia is being firmly positioned as an adjunct to statin therapy, with the ability to enhance the LDL cholesterol lowering efficacy of these agents by 25%.

The combined use of a statin and Zetia as separate pills will have a negative impact on compliance and will increase the cost of lipid lowering therapy. However, the availability of a single pill combination of Zocor and Zetia may address certain of these issues.

The future sales potential of Zetia and its single pill formulation with Zocor may be threatened by third generation statins and developmental compounds with novel mechanisms of action that offer superior potency over marketed anti-dyslipidemics or have anti-atherosclerotic and anti-inflammatory benefits.

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Table of Contents

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EXECUTIVE SUMMARY	4
Introduction	4
Scope and coverage of the Brief	5
Key findings about adjunctive therapies in the market for anti-dyslipidemics	5
PATIENT POTENTIAL	7
Definition of dyslipidemia	7
Segmentation of dyslipidemia	7
Markers for dyslipidemia	7
Which markers are the best indicators of cardiovascular risk?	8
Low HDL cholesterol: a strong predictor, independent of LDL cholesterol	8
BARI trial: importance of non-HDL cholesterol	9
Apolipoprotein B: a better measure of risk than LDL cholesterol?	9
Epidemiology of dyslipidemia	10
Prevalence of hypercholesterolemia	10
Little change in cholesterol among US adults in 1999–2000	12
Prevalence of low HDL cholesterol in the UK	12
UPTAKE OF ADJUNCTIVE THERAPIES	14
Niaspan (niacin)	14
Overview	14
Clinical trial data	15
Commercial potential	15
Advicor (niacin/lovastatin)	18
Overview	18
Clinical trial data	18
Commercial potential	20
WelChol (colesevelam)	22
Overview	22
Clinical trial data	23
Commercial potential	25
THE POTENTIAL FOR ZETIA	28
Zetia (ezetimibe)	28
Drug overview	28
Clinical trial data	29
Ezetimibe as a monotherapy	29
Ezetimibe in combination with statin therapy	30
FACTORS DETERMINING THE ROLE OF ZETIA	34
Factors driving uptake of Zetia	34
Safety concerns over high dose statin therapy	34
Efficacy in difficult-to-treat patients	36
Zetia’s novel mechanism of action	38
Increased patient compliance with the single pill combination therapy	39
Strong marketing support from Merck & Co. to prescribe Zetia in combination with Zocor	40
Factors limiting uptake of Zetia	41
Many patients are adequately controlled on statin monotherapy	41
Widespread availability of cheap, generic statins	42
The launch of more potent third-generation statins	43
Increased cost associated with add-on therapy	44
Increased pill burden with the addition of adjunctive therapy	46
Inability to individually titrate doses in single pill combinations	46
Development of novel adjunctive therapies that have additional anti-atherosclerotic benefits	47
Vascular protectants	47
CETP inhibitors	48
MTP inhibitors	48
CONCLUSION	49
APPENDIX	51
Bibliography	51
Clinical trial data	51
Physician transcripts	52
DISCLAIMER	56
List of Tables
Table 1: Prevalence of hypercholesterolemia in the seven major markets (000s), 2002–10	11
Table 2: Estimated prevalence of low HDL cholesterol (<40mg/dL) in the UK, 2003	13
Table 3: Cost comparison of Advicor single-pill combination versus Niaspan and generic lovastatin components	21
Table 4: Efficacy of WelChol as a monotherapy and in combination in reducing LDL cholesterol and triglyceride levels, and in increasing HDL cholesterol	24
Table 5: Clinical trial results for the use of Zetia as a monotherapy	29
Table 6: Clinical trial results obtained when adding ezetimibe to ongoing statin therapy in patients who had not met LDL cholesterol targets	31
Table 7: Clinical trial results obtained with the concurrent initiation of ezetimibe and statin therapy	32
Table 8: Comparison of Niaspan, Advicor and WelChol	33
Table 9: Factors that may drive of limit the uptake and potential of Zetia	34
Table 10: Number of fatal cases of rhabdomyolysis linked to statin usage in the US in 2001	35
Table 11: Key changes to lipid levels between the NCEP II and NCEP III	38
Table 12: Phase III trial results comparing rosuvastatin with atorvastatin	43
Table 13: Costs of statin monotherapy compared to Zetia/statin combination therapy	45
Table 14: Forecast sales of Zetia ($m), 2003–08	50
List of Figures
Figure 1: Key factors in the market dynamics of Niaspan	17
Figure 2: Advicor: SWOT analysis	22
Figure 3: Key factors in the market dynamics of WelChol	27

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