CRESTORTM (rosuvastatin) Clinical Overview

1
CRESTORTM (rosuvastatin)Clinical Overview
CRESTOR and GALAXY Programme are trade marks of
the AstraZeneca group of companies Licensed from
Shionogi Co. Ltd, Osaka, Japan
2
Contents

• Disease Area Background
• Rosuvastatin Clinical Development Programme
• Efficacy
• Safety and Tolerability
• Clinical Pharmacology
• Rosuvastatin Dosing and Administration
• Rosuvastatin Ongoing Clinical Development

3
Disease Area Background
4
Benefit of Lowering Cholesterol
Meta-analysis of 38 primary and secondary
prevention trials, with more than 98,000 patients
in total
0.0
0.2
Total mortality, p0.04
Mortalitylog oddsratio
0.4
Mortality in CHD, p0.012
0.6
0.8
1.0
0
4
8
12
16
20
24
28
32
Cholesterol reduction ()
Adapted from Gould AL et al. Circulation
199897946952
5
On-Treatment LDL-C is Closely Related to CHD
Events in Statin Trials Lower is Better
30
4S-placebo
2 prevention
25
4S-Rx
20
CHD revasc stroke CHD
Eventrate()
LIPID-placebo
15
LIPID-Rx
CARE-placebo
CARE-Rx
10
HPS-placebo
1 prevention
HPS-Rx
AFCAPS-placebo
WOSCOPS-placebo
5
AFCAPS-Rx
WOSCOPS-Rx
ASCOT-placebo
ASCOT-Rx
0
80
100
120
140
160
180
200
Mean on-treatment LDL-C level at follow-up (mg/dL)
Rxtreatment Adapted from Ballantyne CM. Am J
Cardiol 1998823Q12Q
6
More Effective LDL-C Lowering Improves Patient
Outcomes
All-cause death or major cardiovascular events in
all randomised subjects
Adapted from Cannon C et al. N Engl J Med
20043501495-1504
7
Relationship Between Changes in LDL-C and HDL-C
Levels and CHD Risk
1 decreasein LDL-C reduces CHD risk by1
1 increasein HDL-C reduces CHD risk by3
Third Report of the NCEP Expert Panel. NIH
Publication No. 01-3670 2001. http//hin.nhlbi.nih
.gov/ncep_slds/menu.htm
8
Many Patients in Need of Lipid Lowering Therapy
Remain Untreated EUROASPIRE II
39 untreated
Lipid management assessed in 5556 patients with
CHD at least 6 months after discharge who qualify
for treatment EUROASPIRE II. Eur Heart J
200122554572
9
Many Patients that are Treated are Still not
Getting to Goal
2829 patients
1464 (52) not at goal on starting dose
1365 (48) at goal on starting dose
813 (55) not titrated
651 (45) titrated
448 (69)not at goal
203 (31) at goal
Patients with and LDL-C goal of lt100mg/dL (CHD
and/or diabetes mellitus) with HDL-C 45
mg/dL Foley KA, Simpson RJ, Crouse JR et al. Am
J Cardiol 20039279-81
10
Even With Dose Titration, Many Patients Fail to
Achieve LDL-C Goals The ACCESS Study
At week 54, n2543 CHD patients Ballantyne CM et
al. Am J Cardiol 200188265269
11
Evolution of Lipid Management Guidelines
Driving the Need for More Effective Statin
Therapy
European 2003
European 1994
European 1998
Lower LDL-C goals wider target population need
for more effective therapies.
ATP III 2001
ATP II 1993
ATP I 1988
12
Rosuvastatin Addressing The Unmet Medical Need
in the Treatment of Dyslipidaemia

• A need exists for more efficacious therapy to
  achieve
• greater LDL-C reductions at low dose
• greater LDL-C reductions across the dose range
• more patients to guideline LDL-C goals
• improved HDL-C raising

13
RosuvastatinEfficacy
14
Rosuvastatin reduces LDL-C by up to 63
plt0.001 vs placebo Adapted from Olsson A.
Cardiovasc Drug Rev 200220303328
15
STELLAR - Study Design

• 6 week, randomised, open-label, parallel-group,
  fixed-dose treatment
• 2268 adults with primary hypercholesterolaemia
  
• Randomised to 14 groups
• rosuvastatin 10, 20, 40 mg
• atorvastatin 10, 20, 40 or 80 mg
• simvastatin 10, 20, 40 or 80 mg
• pravastatin 10, 20 or 40 mg
• Pair-wise comparisons of the data
• Percentage change from baseline in lipids
  assessed after 6 weeks of treatment

Adapted from Jones PH et al. Am J Cardiol
200392152160
16
STELLAR - Pair-wise Comparisons
10 mg
20 mg
40 mg
Rosuvastatin
Atorvastatin
80 mg
10 mg
20 mg
40 mg
10 mg
20 mg
40 mg
Rosuvastatin
Simvastatin
10 mg
20 mg
40 mg
Rosuvastatin
Pravastatin
10 mg
20 mg
40 mg
Adapted from Jones PH et al. Am J Cardiol
200392152160
17
Rosuvastatin versus ComparatorsLDL-C Efficacy
Across the Dose RangeThe STELLAR Study
Rosuvastatin Atorvastatin Simvastatin Pravastatin
plt0.002 vs atorvastatin 10 mg simvastatin 10,
20, 40 mg pravastatin 10, 20, 40 mg plt0.002 vs
atorvastatin 20, 40 mg simvastatin 20, 40, 80
mg pravastatin 20, 40 mg plt0.002 vs
atorvastatin 40 mg simvastatin 40, 80 mg
pravastatin 40 mg Adapted from Jones PH et al.
Am J Cardiol 200392152160
18
Rosuvastatin versus Comparators LDL-C Efficacy
at Low Dose The STELLAR Study
plt0.002 vs atorvastatin 10 mg simvastatin 10,
20, 40 mg pravastatin 10, 20, 40 mg plt0.002 vs
atorvastatin 20, 40 mg simvastatin 20, 40, 80
mg pravastatin 20, 40 mg plt0.002 vs
atorvastatin 40 mg simvastatin 40, 80 mg
pravastatin 40 mg Adapted from Jones PH et al.
Am J Cardiol 200392152160
19
Rosuvastatin versus Atorvastatin Consistent
LDL-C Reduction at Low Dose
plt0.001 vs atorvastatin Jones PH et al. Am J
Cardiol 200392152160 Schuster H et al. Am
Heart J 2004 147 705-712 Davidson M et al. Am
J Cardiol 20028926875 Schwartz G et al. Am
Heart J 2004 In Press Olsson AG et al. Am Heart
J 2002144104451 Blasetto JW et al. Am J
Cardiol 200391(Suppl)3C10C
20
Rosuvastatin 10 mg versus Atorvastatin 20 mg
Provides Greater LDL-C Reductions
6 weeks
8 weeks
MERCURY I Schuster
STELLAR Jones
Franken
Jukema
Change in LDL-C from baseline ()
0
n156
n155
n230
n231
n128
n131
n539
n925
-10
-20
-30
-38
-41
-40
-43
-44
-44
-46
-46
-47

ns

-50

Rosuvastatin 10 mg Atorvastatin 20 mg
-60
plt0.05, plt0.001 vs atorvastatin 20 mg
Jones PH et al. Am J Cardiol 200392152160. Schu
ster H et al. Am Heart J 2004147705712.
Franken A et al. Atherosclerosis Supplements
2004 5 (1) 118 Abs M.513. Jukema J et al.
Atherosclerosis Supplements 2004 5 (1) 125 Abs
M.542.
21
Rosuvastatin versus Atorvastatin Achievement of
LDL-C Goals at Low Dose
Rosuvastatin 10 mg vs atorvastatin 10 and 20 mg
patients achieving 2003 European LDL-C goals
LDL-C lt3mmol/l (115mg/dl) in generallt2.5mmol/l
(97mg/dl) for patients with clinically
established CVD or type 2 diabetes
plt0.001 vs atorvastatin 10 mg 20 mg plt0.001
vs atorvastatin 10 mg
1. Schuster H Fox J. Exp Opin Pharmacother
200451187-1200 2. Kritharides L. Eur Heart J
Suppl 2004 6(Suppl A) A12-A18
22
Rosuvastatin vs Simvastatin and
PravastatinAchievement of LDL-C Goals at Low Dose
Rosuvastatin 10 mg vs simvastatin 20 mg and
pravastatin 20 40 mg patients achieving 2003
European LDL-C goals
100
Rosuvastatin
Simvastatin

80

Pravastatin
77
74

60
55
49
40
38
37
20
12
20mg
40mg
20mg
10mg
10mg
11
3
20mg
20mg
10mg
n74
n538
n543
n226
n249
n252
n521
n86
n64
0
20mg
All patients
All patients
Patients with CVD or type 2 diabetes
12 weeks Pooled data Kritharides2
8 weeks MERCURY I Schuster1
LDL-C lt3mmol/l (115mg/dl) in generallt2.5mmol/l
(97mg/dl) for patients with clinically
established CVD or type 2 diabetes
plt0.001 vs simvastatin pravastatin plt0.001 vs
simvastatin pravastatin
1. Schuster H Fox J. Exp Opin Pharmacother
200451187-1200 2. Kritharides L. Eur Heart J
Suppl 2004 6(Suppl A) A12-A18
23
Rosuvastatin versus other statinsAchievement of
LDL-C Goals Across Dose Range
Patients achieving 2003 European LDL-C goals
LDL-C lt3mmol/l (115mg/dl) in general lt2.5mmol/l
(97mg/dl) for patients with clinically
established CVD or type 2 diabetes
Rosuvastatin
plt0.002 vs atorvastatin 10 mg simvastatin 10,
20, 40 mg pravastatin 10, 20, 40 mg plt0.002 vs
atorvastatin 20 mg simvastatin 20, 40 mg
pravastatin 20, 40 mg plt0.002 vs atorvastatin 40
mg simvastatin 40, 80 mg pravastatin 40 mg
Kritharides L. Eur Heart J Suppl 2004 6(Suppl
A) A12-A18
24
Rosuvastatin versus Atorvastatin
Achievement of LDL-C Goal Across Dose Range
Patients achieving NCEP ATP-II LDL-C goals over
52 weeks
p0.006 rosuvastatin 1040 mg vs atorvastatin
1080 mg Olsson AG et al. Am Heart J
2002144104451 Schuster H. Cardiology
200399126139
25
Rosuvastatin versus Atorvastatin
Achievement of LDL-C Goal Across Dose Range
Patients achieving 2003 European LDL-C goal
(lt2.5mmmol/l)
100

90
90
40 mg
18 weeks
83
80 mg
78
20 mg
12 weeks
80
78
77
40 mg
70
70
60
Patients achieving 2003 European LDL-C goal by
dose ()
50
6 weeks
10 mg
20 mg
40
30
20
10
n132
n131
0
Atorvastatin
Rosuvastatin
p0.05 rosuvastatin 40mg vs atorvastatin 80
mg patients with type 2 diabetes and
dyslipidaemia Adapted from Franken A,
Atherosclerosis Supplements 2004 5 (1) 118 Abs
M.513
26
Rosuvastatin versus Atorvastatin
Change in HDL-CThe STELLAR Study
plt0.002 vs atorvastatin 20, 40 and 80
mg plt0.002 vs atorvastatin 40 and 80 mg
Adapted from Jones PH et al. Am J Cardiol
200392152160
27
Rosuvastatin versus Comparators
Change in HDL-C The STELLAR Study
Change in HD-C from baseline ()
plt0.002 vs pravastatin 10 mg plt0.002 vs
atorvastatin 20, 40, 80 mg simvastatin 40 mg
pravastatin 20, 40 mg plt0.002 vs atorvastatin
40, 80 mg simvastatin 40 mg pravastatin 40
mg Observed data in ITT population Adapted from
Jones PH et al. Am J Cardiol 200392152160
28
Rosuvastatin versus Comparators
Change in Triglycerides The STELLAR Study
Dose (mg)
plt0.002 vs pravastatin 10, 20 mg plt0.002 vs
simvastatin 40 mg pravastatin 20, 40 mg plt0.002
vs simvastatin 40 mg pravastatin 40 mg Adapted
from Jones PH et al. Am J Cardiol 200392152160
29
Rosuvastatin Efficacy Summary

• Rosuvastatin is the most effective statin at
  lowering LDL-C
• Rosuvastatin has demonstrated highly effective
  reductions in LDL-C of up to 63
• Rosuvastatin lowers LDL-C significantly more than
  the same and some higher doses of other
  currently marketed statins
• Rosuvastatin 10 mg lowers LDL-C significantly
  more than atorvastatin 10 and 20 mg
• Rosuvastatin 10 mg enables significantly more
  patients to achieve their LDL-C goal than the
  most commonly prescribed doses of other currently
  marketed statins, thereby reducing the need to
  titrate to higher doses
• Rosuvastatin produces a significant increase in
  HDL-C which, unlike atorvastatin, is maintained
  across the dose range

30
Rosuvastatin Tolerability and Safety

• Adverse event profile
• Liver Effects
• Muscle Effects
• Renal Effects

31
Rosuvastatin Clinical Studies Included a Wide
Range of Patients

• Range of patients reflecting those seen in
  general medical practice
• 53 male 47 female (including women of
  childbearing age)
• no upper age limit (31 65 years)
• 17 with type 2 diabetes
• 52 with hypertension
• 36 with overt cardiovascular disease
• 44 with mild renal impairment (8 moderate
  renal impairment)

32
Rosuvastatin Tolerability and Safety - Adverse
Events

• Rosuvastatin is generally well tolerated with an
  adverse event profile similar to currently
  marketed statins
• Most common related adverse events - myalgia,
  asthenia, abdominal pain, nausea these are
  generally mild and transient
• Well tolerated regardless of age, sex, ethnicity,
  presence of co-morbidities or concomitant
  medications
• Similar number of adverse events leading to
  withdrawal (lt3) as other currently marketed
  statins

Brewer HB. Am J Cardiol 200392(Suppl)23K29K
33
Rosuvastatin Tolerability and Safety -
Withdrawals due to Adverse Events
Percentage of patients with an adverse event
leading to withdrawal
Brewer HB. Am J Cardiol 200392(Suppl)23K29K
34
Rosuvastatin Tolerability and Safety - Liver
Effects

• Elevations in liver transaminase levels are an
  infrequent but recognized complication of
  treatment with statins
• Low incidence of clinically significant increases
  in serum transaminases with rosuvastatin 1040
  mg of 0.2 which compares well with that seen
  with other currently marketed statins1
• As with other statins
• liver function tests recommended
• caution in patients who consume excessive
  quantities of alcohol and/or have a history of
  liver disease
• contraindicated in patients with active liver
  disease

ALT gt3 x ULN on 2 successive occasions 1.
Brewer HB. Am J Cardiol 200392(Suppl)23K29K
Please refer to local Prescribing Information
35
Rosuvastatin BenefitRisk Liver Effects ALT
gt3 ULN Frequency by LDL-C Reduction
Persistent elevation is elevation to gt3 x ULN on
2 successive occasions Brewer HB. Am J Cardiol
200392(Suppl)23K29K
36
Rosuvastatin Tolerability and Safety - Muscle
Effects

• As with other statins, effects on skeletal
  muscle, e.g. uncomplicated myalgia, myopathy and,
  rarely, rhabdomyolysis have been reported in
  patients treated with rosuvastatin
• Frequency of treatment-related myopathy in
  clinical trials was lt0.1 in patients treated
  with rosuvastatin up to 40 mg which compares well
  with that seen with other currently marketed
  statins1
• Frequency of rhabdomyolysis with rosuvastatin is
  similar to that reported for the other marketed
  statins2

• defined as CK gt10 ULN plus muscle symptoms
• Brewer HB. Am J Cardiol 200392(Suppl)23K29K
• Data on File
• Please refer to local Prescribing Information

37
Rosuvastatin BenefitRisk - Muscle Effects CK
gt10 x ULN Frequency by LDL-C Reduction
Brewer HB. Am J Cardiol 200392(Suppl)23K29K
38
Rosuvastatin Tolerability and Safety- Renal
Effects
39
Tolerability and Safety - Renal Effects Types of
Proteinuria
40
Rosuvastatin Tolerability and Safety - Proteinuria

• During the clinical development programme
  proteinuria was observed in a small number of
  patients receiving all statin therapies studied
  and placebo1
• This observation was thoroughly investigated in
  rosuvastatin patients. It was found to be usually
  transient, often resolved on continued treatment
  and not predictive of acute or progressive renal
  disease1
• Proteinuria observed with rosuvastatin was
  tubular (reduced reabsorption of normally
  filtered proteins) in origin1
• Development of this tubular proteinuria is likely
  to be a consequence of the pharmacological action
  of rosuvastatin, ie. inhibition of HMG-CoA
  reductase, in the renal tubular cell2,3
• Highly effective inhibition of HMG-CoA reductase
  together with a greater degree of renal excretion
  contribute to this being seen with rosuvastatin

dipstick positive proteinuria defined as a shift
from no protein or trace at baseline to 1.
Vidt DG et al. Cardiology 200410252-60 2.
Sidaway J et al. Toxicology Letters 2003144
(supplement 1)s96 Abs 353 3. Verhulst A et al.
Presented at American Society of Nephrology Nov
2003 Please refer to local Prescribing Information
41
Rosuvastatin Tolerability and Safety -
Proteinuria Frequency of Proteinuria
Treatment Dose n Patients ()
Placebo 330 0.6
Rosuvastatin 10 mg 20 mg 40 mg 1008 872 1850 0.6 0.7 1.2
Atorvastatin 10 mg 20 mg 40 mg 80 mg 628 438 63 342 0.5 0.5 0 0.3
Simvastatin 20 mg 40 mg 80 mg 452 314 325 1.1 0.3 0
Pravastatin 20 mg 40 mg 162 64 0.6 0
dipstick positive proteinuria defined as a shift
from no protein or trace at baseline to
Vidt DG et al. Cardiology 200410252-60
42
Rosuvastatin Tolerability and Safety
Maintenance of Renal Function

• In over 6000 patients receiving rosuvastatin
  (10-40mg) for up to 3.8 years, renal function
  was maintained or tended to improve slightly
• This was evident in all patient groups studied,
  including those at risk of progressive renal
  disease such as the elderly, patients with type 2
  diabetes, hypertension or with pre-existing renal
  dysfunction/proteinuria and also in those who
  developed a positive urine dipstick test during
  the period of treatment

dipstick positive proteinuria defined as a shift
from no protein or trace at baseline to
assessed using derived GFR measurements
Vidt DG et al. Cardiology 200410252-60 Please
refer to local Prescribing Information
43
Rosuvastatin Tolerability and Safety
Maintenance of Renal Function Assessed by GFR
Change in GFR in patients receiving placebo or
rosuvastatin in short-term controlled clinical
trials and long-term open-label treatment
Rosuvastatin 10 mg
Rosuvastatin 20 mg
Rosuvastatin 40 mg
72
n2107 (40 mg)
Placebo
71
71
n109 (40 mg)
n1432 (20 mg)
70
70
70
69
69
n119 (20 mg)
n2909 (10 mg)
68
68
Change in GFR (ml/min/1.73m2)
68
n893 (10 mg)
67
67
67
n371 (placebo)
66
66
65
64
64
64
64
63
Baseline GFR
On-treatment
Baseline GFR
On-treatment
GFR
GFR
Short-term controlled clinical trials (8 weeks)
Long-term open label treatment (gt96 weeks)
plt0.001 for rosuvastatin 10 mg, 20 mg and 40 mg
vs baseline for both short and long-term treatment
Vidt DG et al. Cardiology 200410252-60
44
Rosuvastatin Tolerability and Safety
Maintenance of Renal Function in Different
Patient Groups
Change in GFR in patients receiving long-term
(gt96 weeks) with rosuvastatin 10 mg
6
5
4
Mean change in GFR
(ml/min/1.73m2)
3
2
1
n413
n537
n590
n836
n650
n243
n480
n356
n303
n832
n46
n61
0
gt65
M
N
-ve
lt65
F
Y
N
Y
ve
gt60
lt60
Age, years
Gender
Hypertension
GFR
Type 2
Urine dipstick
diabetes
protein
ml/min/1.73m2 negative is none or trace
positive is gt1 at baseline
Vidt DG et al. Cardiology 200410252-60
45
Rosuvastatin Tolerability and Safety - Renal
Safety Summary

• Rosuvastatin 1040 mg is well tolerated from the
  renal perspective
• Proteinuria was seen in a small number of
  patients receiving all statin therapies studied
  and placebo
• Proteinuria observed with rosuvastatin was
  thoroughly evaluated and found to be mostly
  tubular, usually transient, often resolved on
  continued treatment and not predictive of acute
  or progressive renal disease
• Renal function was maintained or tended to
  improve slightly with long-term treatment

dipstick positive proteinuria defined as a shift
from no protein or trace at baseline to
46
Rosuvastatin - Overall Tolerability and Safety
Summary

• Tolerability profile has been well-researched in
  a large number of patients representing real
  population
• Overall tolerability profile of rosuvastatin
  comparable with currently marketed statins
• Well tolerated with a low rate of withdrawals due
  to adverse events (lt3)
• Adverse events usually mild and transient
• Low incidence of myopathy and of clinically
  significant increases in serum transaminases with
  rosuvastatin 1040 mg, comparable with currently
  marketed statins
• Renal function was maintained or tended to
  improve slightly with long-term treatment
• Favourable benefitrisk profile

47
Rosuvastatin - Experience Since Launch

• As of end April 2004
• Rosuvastatin is approved in over 50 countries
• gt4 million prescriptions issued
• gt1.5 million patients treated
• Benefitrisk profile is consistent with that seen
  in the clinical development programme and
  compares favourably with other currently marketed
  statins

48
Clinical Pharmacology of Rosuvastatin
49
Pharmacokinetic Profile of Selected Statins
Rosuvastatin Atorvastatin Simvastatin Pravastatin
CYP450 3A4 metabolism No Yes Yes No
Clinically significant metabolites No Yes Yes No
Plasma clearance Dual renal / hepatic Primarily hepatic Dual renal / hepatic Dual renal / hepatic
Relatively hydrophilic Yes No No Yes
Hepatoselective Yes Yes Yes Yes
Bioavailability () 20 14 lt5 17
Elimination half-life (hours) 19 14 1.9 77
Elimination T1/2 of drug and metabolites, if
any. CRESTOR (rosuvastatin calcium) Prescribing
Information. Wilmington, DE AstraZeneca
Pharmaceuticals LP 2003. Atorvastatin Calcium
Prescribing Information 2002, Pfizer Inc, NY, NY
Simvastatin Prescribing Information, Merck Co.,
Inc., Whitehouse Station, NJ Pravastatin
Prescribing Information 2003, Bristol-Meyers
Squibb Company, Princeton, NJ.
50
Rosuvastatin - Limited DrugDrug Interactions

• Interactions of no clinical significance
• drugs where metabolism involves cytochrome P450
  such as fluconazole, ketoconazole and traconazole
• fenofibrate
• digoxin
• Interactions with limited clinical significance
• antacid - ? 50 rosuvastatin levels
• erythromycin non-significant ? in rosuvastatin
  plasma levels
• Interactions of clinical significance
• oral contraceptive pill - ? ethinyl oestradiol
  and norgestrel levels which may affect choice of
  oral contraceptive use
• gemfibrozil 2x ? in rosuvastatin plasma levels.
  Combination not recommended
• cyclosporin 7x ? in rosuvastatin plasma levels.
  Combination contraindicated outside of USA
• warfarin ? INR monitoring of INR required

Please refer to local Prescribing Information
51
Rosuvastatin Pharmacokinetics in Special
Populations

• No clinically relevant PK differences
• between younger and elderly (age 65 years)
• between men and women
• between caucasian, hispanic, and black or
  afro-caribbean groups
• in patients with mild to moderate renal
  impairment (creatinine clearance 30
  mL/min/1.73m2)
• PK differences which may influence dose
  selection
• 2-fold increase in AUC in Japanese in Japan and
  Chinese in Singapore compared with Caucasians in
  North America and Europe
• increase in Cmax in moderate/severe hepatic
  impairment
• 3-fold increase in Cmax in severe renal
  impairment (CLcr lt30 mL/min/1.73m2)

Please refer to local Prescribing Information
52
Rosuvastatin Dosing and Administration
53
Rosuvastatin - Dosing and Administration

• Usual start dose 10 mg
• for all patients (new or switch) as it
  effectively gets most patients to their LDL-C
  goal
• Dose range 1040 mg
• Maximum LDL-C response within 4 weeks
• significant response within 2 weeks
• Once daily, any time of day, with or without food

Please refer to local Prescribing Information
54
Ongoing Clinical Development of Rosuvastatin
55
Ongoing Clinical Development - the Rosuvastatin
GALAXY ProgrammeTM

• The GALAXY ProgrammeTM is a large, comprehensive,
  long-term and evolving global research initiative
  sponsored by AstraZeneca investigating
  cardiovascular risk reduction and patient
  outcomes with rosuvastatin
• It has been designed to build on current thinking
  to address important unanswered questions in
  statin research
• Includes studies investigating the effects of
  rosuvastatin on
• atherogenic lipid profile and inflammatory
  markers
• atherosclerosis
• outcomes
• Will provide additional short- and long-term
  efficacy and safety data for rosuvastatin
• Designed to help physicians to improve the
  management of patients with hypercholesterolaemia
  and others with or at risk of cardiovascular
  disease

Schuster H Fox J. Expert Opinion in
Pharmacotherapy 200451187-1200
56
GALAXY ProgrammeTM Studies
GALAXY ProgrammeTM studies with rosuvastatin,
investigating
Atherogenic lipid profile /- inflammatory markers
Atherosclerosis
Reduction in CV morbidity mortality
ORION METEOR ASTEROID
AURORA CORONA JUPITER
STELLAR MERCURY I MERCURY II ORBITAL DISCOVERY
COMETS LUNAR PLUTO POLARIS PULSAR ECLIPSE EXPLORE
R
Schuster H Fox J. Exp Opin Pharmacother
200451187-1200
57
Rosuvastatin has the Largest Number of Outcomes
Studies Ongoing at Launch
STUDY Treatment Subjects Outcome
AURORA Rosuvastatin 10 mg 2700 subjects with end-stage renal disease on chronic haemodialysis1, 2 Mortality and major CV events
CORONA Rosuvastatin 10 mg 4950 patients with heart failure (NYHA class II-IV) of ischaemic aetiology receiving standard treatment1 Mortality and CV events
JUPITER Rosuvastatin 20 mg 15,000 subjects with normal LDL-C levels and raised levels of C-reactive protein1, 3 Primary prevention of CV events
GISSI-HF Rosuvastatin 10 mg or n-3 PUFA (fish oil) 7000 patients with symptomatic heart failure of any aetiology already receiving standard treatment Mortality and morbidity
1. Schuster H Fox J. Exp Opin Pharmacother
200451187-1200 2. Fellström B et al. Nephrol
Dial Transplant 200318(Suppl 4)713 3. Ridker P.
Circulation 200310822922297
58
Rosuvastatin - Overall Summary

• Rosuvastatin produces beneficial effects on key
  lipid parameters at low dose and across the dose
  range
• rosuvastatin is the most effective statin at
  lowering LDL-C
• rosuvastatin 10 mg reduces LDL-C more than the
  same and some higher doses of other currently
  marketed statins
• more patients to LDL-C goal with rosuvastatin 10
  mg than commonly prescribed doses of other
  currently marketed statins, avoiding the need to
  titrate to higher doses
• HDL-C increases maintained across the dose range,
  unlike atorvastatin
• Tolerability and safety profile similar to other
  currently marketed statins
• Low potential for significant drugdrug
  interactions
• A comprehensive clinical development programme is
  ongoing, including a large number of outcomes
  studies