Pipeline Insight Orphan Diseases in CNS Part II Amyotrophic Lateral Sclerosis

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Contributing experts 4
Datamonitor insight into the amyotrophic lateral sclerosis market 4
Key metrics 6
Scenario forecasts for ALS pipeline drugs and total market value 6
Base scenario 7
rhIGF-I /IPLEX successful clinical development scenario 8
Datamonitor pipeline assessment summary 9
Related reports 10
CHAPTER 2 MARKET OVERVIEW 12
Definition of amyotrophic lateral sclerosis 13
Segmentation of amyotrophic lateral sclerosis 13
Etiology 14
Etiology of ALS is largely unknown 14
Prognosis of amyotrophic lateral sclerosis sufferers 15
Epidemiology 16
Diagnosis and treatment rates 17
Diagnosis of ALS-ruling out other diseases first 17
Treatment rates of ALS-the uptake of Rilutek 18
Market size 19
Sizing the ALS market 19
Rilutek (riluzole) 21
Drug overview 21
Clinical trial information 22
Pivotal Rilutek efficacy trial 22
Phase III survival trial 23
Efficacy has broadly been accepted 24
Rilutek sales 24
Rilutek uptake 25
Unmet need in amyotrophic lateral sclerosis 27
Clinical trial design 30
CHAPTER 3 FUTURE MARKET POTENTIAL 31
Scenario forecasts for ALS total market value 32
Base scenario 33
rhIGF-I /IPLEX successful clinical development scenario 34
Forecast Rilutek sales 34
Little switching between Rilutek and new therapies 35
Rilutek patent protection 36
US-Patent US-05527814 should protect Rilutek until 2013 36
5EU-new use patent should protect Sanofi-aventis until late 2012 37
Japan-new use patent should protect Sanofi-aventis until late 2012 37
CHAPTER 4 PIPELINE OVERVIEW AND DYNAMICS 38
Pipeline overview 39
Classification of pipeline products 40
Advantages of developing an ALS treatment 42
NINDS funding of clinical trials 42
For mid-to-large cap companies, ALS offers little risk 43
Indication expansion post-approval for ALS offers future potential 43
Orphan drug designation has additional benefits 43
Current comparator therapy-Rilutek 43
CHAPTER 5 LATE-STAGE DRUG ANALYSIS & FORECASTS 44
Pipeline comparative forecasts 45
Two scenarios have been explored 45
rhIGF-I-recombinant human insulin-like growth factor I 46
Drug overview 46
Forecasts to 2016 47
Base scenario 47
rhIGF-I /IPLEX successful clinical development scenario 48
Datamonitor drug assessment summary-IGF-1/IPLEX successful clinical development scenario 50
Marketing factors-rhIGF-I /IPLEX successful clinical development scenario 51
Marketing of rhIGF-I likely if the NINDS-sponsored trial is successful 51
rhIGF-I will quickly be replaced with the combination product IPLEX 51
Cost of IGF-1 52
Patient potential 53
Satisfaction of unmet needs 54
Better/alternative drugs to slow the progression of the disease 54
Clinical trial data 54
Cochrane Database Systematic Review of rhlGF-1 for ALS 54
First clinical trial investigating the use of rhIGF-I in ALS 55
Smaller negative trial investigating rhIGF-I and ALS 56
Ongoing clinical trial program 56
IPLEX (mecasermin rinfabate, rhIGF-I/IGFBP-3) 57
Drug overview 57
Forecasts to 2016 58
Base scenario 58
IGF-1/IPLEX successful clinical development scenario 59
Datamonitor drug assessment summary-IGF-1/IPLEX successful clinical development scenario 61
IPLEX market penetration-two scenarios 61
Marketing factors 62
Withdrawal from US short-stature market 62
Development for ALS likely to receive a higher priority 62
IPLEX cost and dose 63
IPLEX market penetration-two scenarios 64
Patient potential 64
Satisfaction of unmet needs 64
Clinical trial data 65
Radicut (edaravone, MCI-186) 65
Drug overview-Phase III 65
Lack of clinical data precludes assessment of commercial potential 66
Clinical trial data 66
Ongoing clinical trials 67
E0302 (mecobalamin) 67
Drug overview-Phase II/III 67
Forecasts to 2016-applicable in both forecast scenarios 68
Datamonitor drug assessment summary-IGF-1/IPLEX successful clinical development scenario 69
Marketing factors 69
Cost of E0302 in Japan 69
Uptake of E0302 in Japan 70
E0302/mecobalamin in the ex-Japan markets 70
Patient potential 70
Satisfaction of unmet needs 70
Clinical trial data 70
Ongoing clinical trials 72
Creatine-based preparations 72
ALS-02-creatine monotherapy 72
Drug overview 72
Marketing factors 73
Creatine supplements are widely available over-the-counter 73
Possible advantage of physician monitoring and reimbursement 74
Potential cost and maximum revenue for ALS-02. 74
Patient potential 75
Satisfaction of unmet needs 75
Clinical trial data 76
Maximum voluntary isometric contraction 76
Double-blind trial of survival and disease progression 76
Small trial in advanced ALS patients monitoring respiratory function 77
Clinical trial to examine the muscular effects of creatine in ALS patients 77
Pilot study investigating creatine's effect on muscle strength in ALS patients 78
Ongoing clinical trials 79
ALS-08-creatine in combination with minocycline or celecoxib 79
Minocycline combination shown to be inferior to celecoxib combination 79
Minocycline monotherapy proved to be detrimental to patients 79
Celecoxib combination-non-futile compared to historical controls 80
Celecoxib monotherapy trial-no clear efficacy as a monotherapy 80
Arimoclomol 81
Drug overview-Phase II 81
Clinical trial data 82
Multi-center Phase IIa clinical trial monitoring safety and tolerability of arimoclomol 82
Open-label extension clinical trial of arimoclomol in ALS 82
Ongoing clinical trial program 83
Other ALS pipeline drugs 84
FP-0011 84
Drug overview-Phase II 84
Clinical trial data 84
Cereact 85
Drug overview 85
Clinical trial data 85
Talampanel 86
Copaxone (glatiramer acetate) 86
KNS-760604 (R-pramipexole) 87
Ceftriaxone 88
Coenzyme Q10 88
BIBLIOGRAPHY 89
Journals 89
Websites 94
Datamonitor reports 99
APPENDIX A 100
Methodology 100
Datamonitor forecast methodology 100
Product forecasts 100
Definition of a Standard Unit 100
Contributing experts 102
APPENDIX B 103
About Datamonitor 103
About Datamonitor Healthcare 103
Datamonitor Healthcare's therapy area capabilities 104
About the Disease analysis team 105
Disclaimer 106
List of Tables
Table 1: Prevalence estimates of ALS across the 7MM, 2007 17
Table 2: Rilutek uptake in the three major market regions, 2006 26
Table 3: Cost of Rilutek (riluzole), 2006/07 27
Table 4: Key late-stage R&D pipeline in ALS, 2007 39
Table 5: Drug classes and modes of action for key ALS pipeline drugs 40
Table 6: Estimated cost of Rilutek, Avonex and rhIGF-I , 2006 53
Table 7: Datamonitor drug assessment parameters 101
List of Figures
Figure 1: ALS market size and forecast-base scenario, 2006-16 7
Figure 2: ALS market size and forecast-IGF-1/IPLEX scenario, 2006-16 8
Figure 3: Drug assessment summary for ALS treatments - IGF-1/IPLEX successful clinical development scenario, 2007 9
Figure 4: Total ALS market sales revenue ($m), 2003-06. 20
Figure 5: Prescription revenue versus prescription volume of Rilutek and other drugs in the seven major ALS markets, 2006 21
Figure 6: Rilutek revenue by market, 2006 25
Figure 7: Key unmet needs in ALS treatment 28
Figure 8: ALS market size and forecast-base scenario, 2003-2016 33
Figure 9: ALS market size and forecast-IGF-1/IPLEX scenario, 2003-2016 34
Figure 10: Percentage change in Rilutek sales in the US Q3 2002 to Q2 2007 35
Figure 11: Rilutek sales revenue forecast across the 7MM, 2007-16 36
Figure 12: Origin of ALS key late-stage pipeline drugs, 2007 42
Figure 13: Forecast sales revenue for key ALS pipeline drugs, 2007-16 46
Figure 14: rhIGF-I sales revenue forecast based on the rhIGF-I /IPLEX successful clinical development scenario, 2007-16 49
Figure 15: Datamonitor's drug assessment summary for rhIGF-I 50
Figure 16: IPLEX base scenario ALS sales revenue forecast, 2007-16. 59
Figure 17: IPLEX sales revenue forecast, rhIGF-I/IPLEX successful clinical development scenario, 2007-16 60
Figure 18: Datamonitor's drug assessment summary for IPLEX 61
Figure 19: E0302 (mecobalamin) ALS sales forecast, 2007-16 68
Figure 20: Datamonitor's drug assessment summary for E0302 (mecobalamin) 69
Figure 21: Datamonitor drug assessment summary of pipeline molecular targeted therapies in development for hematological malignancies, 2007 102