Drugs of Tomorrow 2002: Leukemia

The innovative products represent approximately two thirds of the compounds in development for leukemia. With a limited patient population and increasing costs of R&D and manufacture, a high price-point is likely to be attached to a therapeutic launched into the leukemia market. With the success of Novartis’ Gleevec (imatinib mesylate) exhibiting strong sales growth where unmet therapeutic need has driven market uptake regardless of its high price point, the drug is acting as proof to the industry that the leukemia’s offer high returns.

Drug analysis: Cytotoxic therapies (covering the new cytotoxic compounds in development)

Supergen’s decitabine is likely to show significant uptake due to its strong efficacy and favorable side-effect profile. In addition, Shire’s Troxatyl (troxacitabine) appears to be another strong candidate that is likely to perform well, especially when taking into account shires established sales force. As the current cytotoxic regimes used in leukemia treatment are generally older, off-patent treatments, the new compounds in development displaying highly favorable increases in efficacy and beneficial side-effect profiles, such as decitabine and Troxatyl, are likely to drive off-label usage in the acute leukemias.

Within the development pipeline, the chemopotentiators will drive sales growth through potentiating existing first-line regimens. With the high level of therapeutic unmet need, where some acute leukemia regimens are 15 years old, the potentiation of existing therapies will drive additional sales growth in a similar manner to Novartis’ Gleevec. Of key interest is Genta’s Genasense (augmerosen), an antisense inhibitor that potentiates the majority of existing cytotoxic compound classes in cancers expressing the Bcl-2 protein. With Aventis as a marketing partner, Genasense is likely to exhibit a high price-point and strong off-label usage that will drive its sales to blockbuster potential.

Table 1: The positive an negative drivers of the leukemia market, 2002-2010 8

Table 2: Forecast sales of the leukemia pipeline drugs, 2002-2010 9

Table 3: Overview of the leukemia market, 2002 10

Table 4: Current gold-standard therapies for adult leukemia, 2002 30

Table 5: Cytotoxic agents commonly used in the management of leukemia 31

Table 6: The number of compounds within each drug class, per developmental stage, 2002. 59

Table 7: Breakdown of innovative pipeline drugs for leukemia 60

Table 8: The number of leukemia drugs in development by region 67

Table 9: List of companies with products in the pipeline for leukemia 76

Table 10 Reference for drug summary tables 81

Table 11: The pipeline cytotoxics for leukemia, 2002 82

Table 12: Decitabine’s satisfaction of unmet needs 88

Table 13: Global forecasts for decitabine, 2002-2010 90

Table 14: Overall response toward homoharringtonine as a combination therapy with interferon-alpha 93

Table 15: Homoharringtonine’s satisfaction of unmet needs 97

Table 16: Prior therapeutic regimens 100

Table 17: The numbers of patient exhibiting specific side-effects and their severity 100

Table 18: The numbers of patient exhibiting specific side-effects and their severity 101

Table 19: Troxacitabine side-effects and severity in relapsed patients 102

Table 20: Troxatyl’s satisfaction of unmet needs 105

Table 21: Global forecasts for Troxatyl, 2002-2010 107

Table 22: Global forecasts for Clofarex, 2002-2010 112

Table 23: Summarized clinical trial results for all the cytotoxic compounds profiled 117

Table 24: Additional indications being targeted by the profiled cytotoxic compounds 118

Table 25: Global sales forecasts for the cytotoxic therapies for leukemia (2002-2010) 121

Table 26: Abbreviations within Tables 18-20 123

Table 27: Innovative therapies in phase III development 124

Table 28: Innovative therapies in phase II development 125

Table 29: Innovative therapies in phase I, preclinical and discovery developmental phases 126

Table 30: Ceplene’s satisfaction of unmet needs 133

Table 31: Global forecasts for Ceplene, 2002-2010 135

Table 32: Zamyl’s satisfaction of unmet needs 143

Table 33: Genasense’s satisfaction of unmet needs 149

Table 34: Global forecasts for Genasense, 2002-2010 151

Table 35: PEG-Intron’s satisfaction of unmet needs 156

Table 36: Global forecasts for PEG-Intron, 2002-2010 158

Table 37: Exatecan’s satisfaction of unmet needs 163

Table 38: Global forecasts for exatecan, 2002-2010 165

Table 39: Global forecasts for GVAX, 2002-2010 172

Table 40: Global forecasts for Thalomid, 2002-2010 180

Table 41: Global forecasts for E21R, 2002-2010 186

Table 42: Summarized clinical trial results, for leukemia indications, for all the innovative compounds profiled 191

Table 43: Additional indications being targeted by the profiled innovative compounds 193

Table 44: Global sales forecasts for the innovative therapies, for leukemia (2002-2010) 195

Table 45: List of companies with products in the pipeline for leukemia 207

Table 46: Forecast leukemia market size by 2010 208

Table 47: Global sales forecasts for the innovative therapies, for leukemia (2002-2010) 208

Figure 1: Forecast revenues within the leukemia market, 2001- 2010 8

Figure 2: Defining the leukemia patient population, 2002 24

Figure 3: Unmet needs in leukemia, 2000 40

Figure 4: Schematic representation of biotech business model transition through sales force establishment 46

Figure 5: Revenue growth through successive product launches, with time and increases in sales force size 47

Figure 6: Potential endpoints in leukemia clinical trials and impact on drug development 48

Figure 7: Revenue streams derived from various endpoints in leukemia drug development 49

Figure 8: Schematic representation of the impact of reformulation on the market 51

Figure 9: Breakdown of the R&D pipeline by licensing status in the cytotoxic market for leukemia. 53

Figure 10: The breakdown of the R&D pipeline by licensing status in the innovative market for leukemia. 55

Figure 11: The proportion of licensing routes per phase of development, across all leukemia drug classes, 2002. 58

Figure 12: The clinical and commercial benefits of the antisense pipeline in leukemia and why it is suited to the biotechnology industry 62

Figure 13: Schematic representation of increasing GVAX’s treatment longevity (per patient) over potential competition 64

Figure 14: Multi-tiered chart depicting the product classes by therapeutic phase 66

Figure 15: The numbers of compounds being developed per region 69

Figure 16: Proportion of originator company types with leukemia drugs in development 71

Figure 17: Profile of agreement type, per developmental phase made with the originator companies 72

Figure 18: Analysis of the leukemia pipeline by company type and time-to-market, 2002 75

Figure 19: Schematic representation of the effect of an accelerated approval on a products revenue potential and life-cycle 78

Figure 20: The relationship between the number of drugs in development by the biotechnology sector versus those of the large ethical pharma houses. 79

Figure 21: Key factors in the relative success of decitabine 89

Figure 22: Key factors in the relative success of homoharringtonine 98

Figure 23: Key factors in the relative success of Troxatyl 106

Figure 24: Key factors in the relative success of Clofarex 111

Figure 25: Comparison of the key cytotoxic treatments profiled, regarding the compounds market anticipation and therapeutic benefits 114

Figure 26: Comparison of the key cytotoxic treatments profiled, regarding the company’s marketing ability and the likelihood of gaining market share 115

Figure 27: Strategic sales and marketing options available to Maxim for Ceplene 131

Figure 28: Key factors in the relative success of Ceplene 134

Figure 29: Key factors in the relative success of Zamyl 144

Figure 30: Key factors in the relative success of Genasense 150

Figure 31: Key factors in the relative success of PEG-Intron 157

Figure 32: Key factors in the relative success of exatecan 164

Figure 33: Key factors in the relative success of GVAX 171

Figure 34: Key factors in the relative success of Thalomid 179

Figure 35: Key factors in the relative success of E21R 185

Figure 36: Comparison of the key innovative treatments profiled, in relation to the market anticipation and therapeutic benefits surrounding the product developments 187

Figure 37: Comparison of the key innovative treatments profiled, in relation to the company’s marketing ability and the likelihood of gaining market shares 188

Figure 38: Datamonitor’s Healthcare Consultancy 216