Table of Contents

ABOUT DATAMONITOR HEALTHCARE

2

About the Respiratory and Infectious Diseases pharmaceutical analysis team

2

CHAPTER 1 EXECUTIVE SUMMARY

3

Objective of the analysis

3

Datamonitor insight into the Hospital Antibacterials market

4

Generic incursion bites hard

4

MRSA saturation: But what about the Gram- negatives?

4

IV generics: escaping the oral market rush

5

CHAPTER 2 MARKET DEFINITION AND OVERVIEW

8

Market definition for this report

8

Setting of treatment decision

8

Route of antibiotic administration

10

Classification of antibiotic treatments

10

Core Market branded product coverage

11

Late-stage pipeline coverage

14

Current market situation

15

A declining market with increasing needs

15

Total Market value

16

Core Market situation

17

Core Market dynamics versus Total hospital market contributors

23

Key players in the hospital antibacterials market

26

Marketed product coverage

31

Core Market branded product coverage

31

Carbapenems

32

Core Market coverage

32

Class overview

33

Core Market brand overviews

37

Core Market comparative forecasts

44

Cephalosporins

46

Core Market coverage

46

Class overview

46

Core market brand overviews

53

Core Market comparative forecasts

56

Fluoroquinolones

58

Core Market coverage

58

Class overview

58

Core Market brand overviews

64

Core Market comparative forecasts

70

Glycopeptides

72

Core Market coverage

72

Class overview

72

Core Market brand overviews

76

Core Market comparative forecasts

78

Penicillins

81

Core Market coverage

81

Class overview

81

Core Market brand overviews

84

Core Market comparative forecasts

87

Others

90

Core Market coverage

90

Core Market brand overviews

93

Core Market comparative forecasts

99

CHAPTER 3 COUNTRY MARKET ASSESSMENTS

103

7MM

103

Key Facts

103

Opportunities and threats

105

Pharmacoeconomic analysis: Influencing key decision makers

106

The rise and rise of problematic pathogens

114

United States

124

Key facts

124

Market Overview

124

Top 10 Brands - US market leaders by volume and value sales

125

Class shares - Cephalosporin and fluoroquinolone class erosion

128

Heavy brand preference, even IV/Oral split

129

Opportunities and threats

131

Broader FDA initiatives decrease time to market, but antibiotic scrutiny increases

132

DTC advertising - ideal for the acute sector, but not for Hospital Antibacterials

133

Pricing and reimbursement

134

Prescription Drug User Fee Act (PDUFA) could reduce Net Present Value (NPV) further

136

Japan

137

Key facts

137

Market Overview

138

Top 10 Brands - Japanese market leaders by volume and value sales

138

Class shares - a heavy β-lactam bias

141

Genericisation still slow, oral formulations prefered

141

Opportunities and threats

143

The threat of foreign competition: enough to force domestic change?

144

Price cuts - still dominating pricing and reimbursement in Japan

146

Increasing uptake of generics

147

Lengthy approval process slows down access to the Japanese market

148

5EU

148

Key facts

148

Market Overview

149

Top 10 Brands - M5EU market leaders by volume and value sales

149

Class Share - evenly spread sales

152

High generic penetration, with an IV bias

153

Opportunities and Threats

155

EMEA drug approval process harmonization

155

Smaller companies helped by European regulators

157

France

158

Sales overview

158

Opportunities and threats

160

Germany

164

Sales overview

164

Opportunities and threats

166

Italy

170

Sales Overview

171

Opportunities and threats

173

Spain

177

Sales Overview

177

Opportunities and threats

179

United Kingdom

183

Sales overview

183

Opportunities and Threats

185

CHAPTER 4 R&D APPROACH

192

Clinical trial design in serious bacterial infections

192

Target patient groups

193

Site of infection

193

The spectrum dilemma

194

Choosing clinical trial objectives: what not to measure?

196

Overview of pipeline products

201

Class 1: Glycopeptides

201

Zeven (dalbavancin)

203

Arbelic (telavancin)

216

Oritovancin

223

Class 2: Cephalosporins

231

Ceftaroline fosamil

232

Ceftobiprole medocaril

236

Class 3: Other antibacterials

243

Iclaprim

243

Aztreonam

247

CHAPTER 5 FORECAST ANALYSIS

248

General assumptions

248

IV/Oral genericization

248

Pricing of generics and level of generic incursion

248

Key events

249

Product Launches: Sequence of Events and Key Assumptions

249

Cubicin

249

Tygacil

250

Zeven

251

Arbelic

252

Finibax

253

Ceftobiprole

253

Iclaprim

254

Ceftaroline

255

Patent expiries: sequence of events and key assumptions

256

Rocephin knock on effects

256

Zosyn

257

Maxipime

258

Merrem

258

Synercid

259

Tequin

259

Levaquin

260

Invanz

260

Tygacil

261

Zyvox Oral/IV

261

Avelox

262

Usage expansion

263

Rise of Gram-negatives

263

Inhaled Aztreonam

264

Cubicin

264

Invanz

265

Tygacil

266

Arbelic

267

Iclaprim

267

Other events

268

Tequin

268

Fluoroquinolones

268

Data definitions, limitations and assumptions

269

Standard units

269

Japanese market data

269

Derivation of sales forecasts and pricing trends

269

Forecasts

270

Forecast methodology

270

CHAPTER 6 APPENDIX A - MARKET DATA AND MAJOR BRAND KEY FACTS

271

Summary data for the hospital antibiotics market

271

Carbapenem market data

276

Primaxin

276

Merrem

277

Invanz

278

Finibax

279

Cephalosporin market data

280

Claforan

280

Maxipime

281

Fluoroquinolone market data

282

Levaquin

282

Cipro

283

Avelox

284

Tequin

285

Glycopeptide Market Data

286

Vancocin

286

Targocid

287

Others

288

Cubicin

288

Zyvox (IV&Oral)

289

Synercid

290

Tygacil

291

CHAPTER 7 APPENDIX B - MARKET FORECAST DATA

292

Seven major markets

292

US

298

Japan

304

5EU

309

France

315

Germany

321

Italy

327

Spain

333

UK

338

CHAPTER 8 APPENDIX C

344

Bibliography

344

Books

344

Epidemiology

344

Clinical trial data

346

Pharmacoeconomic studies

352

Other

352

Report methodology

353

Abbreviations

354

About Datamonitor

356

About Datamonitor Healthcare

356

About the Antibacterials analysis team

357

Key therapy team members

358

Holger Rovini, Head of Respiratory and Infectious Diseases

358

Disclaimer

359

List of Tables

Table 1: Marketed antimicrobial products by ATC class and groupings used in this report, 2007

12

Table 2: Late-stage pipeline antibiotic products by trial phase, indication and grouping, 2007

14

Table 3: Indexed Total Market sales by brand 2003-06, Sales by value 2006 ($m), seven major markets

19

Table 4: Indexed Total Market hospital sales by class, volume and value, 2003-06, seven major markets

20

Table 5: Indexed brand, generic, IV and oral sales for Core Market products (volume and value), 2003-06, seven major markets

23

Table 6: Top 10 seven major market hospital antibacterials leaders by sales of Core Market branded products ($m), 2006

28

Table 7: Total Market carbapenem sales by volume and value sales and market growth by geographic region (US, Japan, 5EU), 2003-06

35

Table 8: Indexed Total Market carbapenem value sales, 2003-06, seven major markets

37

Table 9: Cephalosporins' spectrum of activity by generation

48

Table 10: Total Market cephalosporin sales by volume and value sales and market growth by geographic region (US, Japan, 5EU), 2003-06

50

Table 11: Indexed Total Market cephalosporin volume and value sales, 2003-06, seven major markets

51

Table 12: Indexed brand, generic, IV and oral sales for Core Market cephalosporins (volume and value), 2003-06, seven major markets

52

Table 13: Total Market fluoroquinolone sales by volume and value sales and market growth by geographic region (US, Japan, 5EU), 2003-06

61

Table 14: Indexed Total Market fluoroquinolone value sales, 2003-06 seven major markets

62

Table 15: Indexed Core Market brand, generic, IV and oral sales for cephalosporins (volume and value),( 2003-06, seven major markets

64

Table 16: Total Market glycopeptide sales by volume and value sales and market growth by geographic region (US, Japan, 5EU), 2003-06

74

Table 17: Indexed Total Market branded and generic glycopeptides sales by value, 2003-06, seven major markets

75

Table 18: Total Market penicillin sales by volume and value sales and market growth by geographic region (US, Japan, 5EU), 2003-06

83

Table 19: Indexed Total Market branded and generic Penicillins, volume and value sales and pricing, 2003-06

84

Table 20: Total Market "Others" sales by volume and value sales and market growth by geographic region (US, Japan, 5EU), 2003-06

91

Table 21: Indexed Total Market branded and generic others, volume and value sales and pricing, 2003-06

92

Table 22: 7MM Leading brands by value sales 2006 ($m) and CAGR growth (2003-2006)

104

Table 23: 7MM top ten brands by volume sales 2006 ($m) and CAGR growth (2003-2006)

104

Table 24: Global Opportunities and Threats

105

Figure 29: Healthcare spending as a proportion of GDP in the 7MM, 2004

107

Table 25: Relative Net Present Value (NPV) by therapy area

121

Table 26: US Top Ten brands by 2006 sales value ($m) and CAGR (2003-2006)

126

Table 27: US Top Ten brands by 2006 sales volume (SUm) and CAGR (2003-2006)

126

Table 28: US Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

127

Table 29: Core US market branded, generic, oral and IV volume and value share 2003-2006 (%)

130

Table 30: United States summary of opportunities and threats

131

Table 31: Japanese Top Ten brands by 2006 sales value ($m) and CAGR (2003-2006)

139

Table 32: Japanese Top Ten brands by 2006 sales volume (SUm) and CAGR (2003-2006

139

Table 33: Japan Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

140

Table 34: Japan summary of opportunities and threats

143

Table 35: M5EU Top Ten brands by 2006 sales value ($m) and CAGR (2003-2006)

150

Table 36: M5EU Top Ten brands by 2006 sales volume (SUm) and CAGR (2003-2006)

150

Table 37: M5EU Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

151

Table 38: Indexed Total Market growth in the M5EU, 2003-2006, value and volume shares, 2006 sales ($m) and CAGR 2003-2006

153

Table 39: Indexed Core Market M5EU branded, generic, oral and IV value share 2003-2006

154

Table 40: 5EU Opportunities and Threats

155

Table 41: France Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

159

Table 42: France Opportunities and Threats

160

Table 43: Germany Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

165

Table 44: Germany Opportunities and Threats

166

Table 45: Italy Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

172

Table 46: Italy - Opportunities and Threats

173

Table 47: Spain Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

178

Table 48: Spain - Opportunities and Threats

179

Table 49: UK Total Market Indexed Sales by Brand 2003-2006, Sales by value 2006 ($m)

184

Table 50: UK Opportunities and Threats

185

Figure 51: Clinical trial issues in severe bacterial infections

193

Table 51: Late-stage pipeline hospital antibacterial agents. 2007

201

Table 52: Dalbavancin: summary information

203

Table 53: Telavancin: summary information

216

Table 54: Oritavancin: summary information

223

Table 55: Ceftaroline fosamil: summary information

232

Table 56: Ceftobiprole medocaril: summary information

236

Table 57: Iclaprim: summary information

243

Table 58: Cubicin Launch

249

Table 59: Tygacil Launch

250

Table 60: Zeven Launch

251

Table 61: Arbelic Launch

252

Table 62: Finibax Launch

253

Table 63: Ceftobiprole Launch

253

Table 64: Iclaprim Launch

254

Table 65: Ceftaroline Launch

255

Table 66: Rocephin Patent Expiry: Knock on Effects

256

Table 67: Zosyn patent expires 2007/7, Generics launch after petition settlement2008/03

257

Table 68: Maxipime

258

Table 69: Merrem Patent expiry

258

Table 70: Synercid Patent Expiry

259

Table 71: Tequin Patent Expiry

259

Table 72: Levaquin IV patent expiry

260

Table 73: Invanz patent expiry

260

Table 74: Tygacil Patent Expiry

261

Table 75: Zyvox Oral/IV patent expiry

261

Table 76: Avelox IV/Oral: patent expiry

262

Table 77: Rise of Gram-negatives

263

Table 78: Inhaled Aztreonam approved for Cystic Fibrosis RTIs

264

Table 79: Cubicin: Expansion to Endocarditis, Off-label EU use in bacteremia

264

Table 80: Invanz: Additional indication of prophylaxis of surgical site infections in colorectal surgery

265

Table 81: Tygacil

266

Table 82: Telavancin

267

Table 83: Iclaprim

267

Table 84: Tequin

268

Table 85: Fluoroquinolones: safety concerns

268

Table 86: 7MM Total Market Summary Data

271

Table 87: US Total Market Summary Data

271

Table 88: Japan Total Market Summary Data

272

Table 89: 5EU Total Market Summary Data

272

Table 90: France Total Market Summary Data

273

Table 91: Germany Total Market Summary Data

273

Table 92: Italy Total Market Summary Data

274

Table 93: Spain Total Market Summary Data

274

Table 94: United Kingdom Total Market Summary Data

275

Table 95: Primaxin: key facts

276

Table 96: Merrem: key facts

277

Table 97: Invanz: key facts

278

Table 98: Finibax: key facts

279

Table 99: Claforan: key facts

280

Table 100: Maxipime: key facts

281

Table 101: Levaquin: key facts

282

Table 102: Cipro: key facts

283

Table 103: Avelox: key facts

284

Table 104: Tequin: key facts key facts

285

Table 105: Vancocin: key facts

286

Table 106: Targocid: key facts

287

Table 107: Cubicin: key facts

288

Table 108: Zyvox: key facts

289

Table 109: Synercid: key facts

290

Table 110: Tygacil: key facts

291

Table 111: Datamonitor forecasts for core market hospital antibiotics in the 7MM to 2016 ($m)

292

Table 112: Datamonitor forecasts for core market hospital antibiotics in the US to 2016 ($m)

298

Table 113: Datamonitor forecasts for core market hospital antibiotics in the Japan to 2016 ($m)

304

Table 114: Datamonitor forecasts for core market hospital antibiotics in the 5EU to 2016 ($m)

309

Table 115: Datamonitor forecasts for core market hospital antibiotics in the France to 2016 ($m)

315

Table 116: Datamonitor forecasts for core market hospital antibiotics in the Germany to 2016 ($m)

321

Table 117: Datamonitor forecasts for core market hospital antibiotics in the Italy to 2016 ($m)

327

Table 118: Datamonitor forecasts for core market hospital antibiotics in the Spain to 2016 ($m)

333

Table 119: Datamonitor forecasts for core market hospital antibiotics in the UK to 2016 ($m)

338

List of Figures

Figure 1: Defining the market - acquisition, onset and treatment settings for severe bacterial infections

9

Figure 2: Pharmaceutical sales across the seven major markets ($ billion), 2006

15

Figure 3: Indexed Total Market sales by class, volume and value, 2003-06, seven major markets

20

Figure 4: Indexed brand, generic, IV and oral sales for Core Market products (volume and value), 2003-06, seven major markets

22

Figure 5: Total Market versus Core Market coverage by class, volume and value, 2006, seven major markets

24

Figure 6: Core Market versus Rest of Market volume and value growth rates (%), 2003-06, seven major markets

25

Figure 7: Core Market versus Rest of Market coverage versus Rest of Market by class, volume and value, 2006

26

Figure 8: Top 10 seven major market hospital antibacterials leaders by sales of Core Market branded products (%), 2006

27

Figure 9: Total Market carbapenem sales by volume and value sales by geographic region (US, Japan, 5EU), 2003-06

35

Figure 10: Indexed Total Market carbapenem sales by volume and value, 2003-06, seven major markets

36

Figure 11: Core Market Carbapenem volume and value forecasts, 2006*-2016

45

Figure 12: Total Market cephalosporin sales by volume and value sales by geographic region (US, Japan, 5EU), 2003-06

49

Figure 13: Indexed Total Market Cephalosporin sales by volume and value, 2003-06, seven major markets

50

Figure 14: Indexed brand, generic, IV and oral sales for Core Market cephalosporins (volume and value), 2003-06, seven major markets

52

Figure 15: Core Market Cephalosporin volume and value forecasts, 2006*-2016

56

Figure 16: Total Market fluoroquinolone sales by volume and value sales by geographic region (US, Japan, 5EU), 2003-06

61

Figure 17: Indexed Total Market fluoroquinolone sales by volume and value, 2003-2006, seven major markets

62

Figure 18: Indexed Core Market brand, generic, IV and oral sales for fluoroquinolones (volume and value),( 2003-06, seven major markets

63

Figure 19: Core Market fluoroquinolone volume and value forecasts, 2006*-2016

70

Figure 20: Total Market glycopeptide sales by volume and value sales by geographic region (US, Japan, 5EU), 2003-06

74

Figure 21: Indexed Total Market branded and generic glycopeptides, volume and value sales and pricing, 2003-06, seven major markets

75

Figure 22: Core Market glycopeptide volume and value forecasts, 2006*-2016

78

Figure 23: Total Market penicillin sales by volume and value sales by geographic region (US, Japan, 5EU), 2003-06

82

Figure 24: Total Market penicillin sales by volume and value sales, 2003-06

83

Figure 25: Core Market Penicillin volume and value forecasts, 2006*-2016

88

Figure 26: Total Market "Others" sales by volume and value sales by geographic region (US, Japan, 5EU), 2003-06

91

Figure 27: Indexed Core Market branded and generic Others volume and value sales and pricing, 2003-06

92

Figure 28: Core Market Others volume and value forecasts, 2006*-2016

100

Figure 30: Key pricing controls used globally, 2006

108

Figure 31: Total cost of care - beyond antibiotic costs

110

Figure 32: Stakeholder balance of power

111

Figure 33: Data relevance to stakeholders

112

Figure 34: Audience-targeted pharmacoeconomic data

113

Figure 35: Pharmacoeconomic impact of antibiotic policies in the treatment of ventilator associated pneumonia

114

Figure 36: Net Present Value - why the antibiotic pipeline suffers

119

Figure 37: Relative Net Present Value by therapy area

120

Figure 38: Incentivizing antibiotic R&D - optimizing returns and reducing costs

121

Figure 39: Indexed Total Market growth in the US in the hospital antibacterials market, 2003-06, value and volume share (%)

129

Figure 40: Core Market US branded, generic, oral and IV hospital antibacterials, volume and value share (%), 2003-06

130

Figure 41: Decrease of FDA's mean total approval time

132

Figure 42: Indexed Total Market growth in the hospital antibacterials market in Japan, value and volume share (%), 2003-06

141

Figure 43: Core Market Japanese branded, generic, oral and IV hospital antibacterials volume and value share (%), 2003-06

142

Figure 44: Indexed Total Market growth in the hospital antibacterials market in the 5EU, value and volume share (%), 2003-06

152

Figure 45: Core Market 5EU branded, generic, oral and IV hospital antibacterials volume and value share (%), 2003-06

154

Figure 46: Core France market branded, generic, oral and IV volume and value share 2003-2006 (%)

161

Figure 47: Core German market branded, generic, oral and IV volume and value share 2003-2006 (%)

170

Figure 48: Core Italian market branded, generic, oral and IV volume and value share 2003-2006 (%)

175

Figure 49: Core Spanish market branded, generic, oral and IV volume and value share 2003-2006 (%)

182

Figure 50: Core UK market branded, generic, oral and IV volume and value share 2003-2006 (%)

187

Figure 52: The spectrum dilemma - pros and cons of broad versus specialist indication trial design

195

Figure 53: Typical Phase III trial inclusion and exclusion criteria

196

Figure 54: The spectrum dilemma: broad versus narrow applicability

198

Figure 55: Dalbavancin Phase II trial in complicated Skin and Soft Tissue Infections

207

Figure 56: Dalbavancin Phase II trial in Catheter-Related Blood Stream Infections

208

Figure 57: Dalbavancin Phase III trial in complicated Skin and Soft Tissue Infections versus Linezolid

210

Figure 58: Dalbavancin Phase III trial in Skin or Soft Tissue Infections, versus IV and Oral Cephalosporins

211

Figure 59: Dalbavancin Phase III trial in Skin or Soft Tissue Infections versus vancomycin

212

Figure 60: Telavancin Phase III trial in complicated Skin and Skin Structure Infections versus vancomycin

220

Figure 61: Oritavancin Phase III trials in complicated Skin and Skin Structure Infections versus vancomycin and oral cephalexin

226

Figure 62: Oritavancin Phase III trials in complicated Skin and Skin Structure Infections versus vancomycin and oral cephalexin

228

Figure 63: Ceftobiprole Phase III trial in complicated Skin and Skin Structure Infections versus vancomycin

240