Forecast Insight: Epilepsy - Future market upgrade following new drug launches
Introduction
Driven primarily by continued uptake of UCB's market leading anticonvulsant, Keppra (levetiracetam), seven major market epilepsy revenues grew strongly at a compound annual growth rate of 11.7% to reach almost $3.8 billion in 2007.
Scope
*This report gives a strategic analysis of the likely impact that recent events will have on the future epilepsy market
*Includes epilepsy-specific sales forecasts for the key brands, generics, and pipeline agents in the seven major markets to 2017
*Provides a global market snapshot by including epilepsy-specific sales analysis for leading brands outside the seven major markets
*Key conclusions are supported by key opinion leader comment
Highlights
Despite the failure of UCB's brivaracetam to meet its primary endpoint in a Phase III trial in Unverricht Lundborg disease, the drug is expected to receive strong uptake in patients with refractory partial-onset seizures. Interviewed key opinion leaders remain optimistic about brivaracetam's future prospects.
As a result of Valeant's August 2008 collaboration with GlaxoSmithKline and the release of positive Phase III clinical trial data in September 2008, Datamonitor has upgraded its epilepsy-specific sales forecast for retigabine. However, the drug's likely three-times daily dosing is not expected to be well received by patients and physicians.
D-Pharm's DP-VPA (a prodrug of valproic acid), has not made any known progress through clinical development since 2006. As a result, launch of DP-VPA is expected to take place 1 year later than what was estimated in Datamonitor's previous epilepsy market report and epilepsy-specific sales forecasts for the drug have been downgraded.
Reasons to Purchase
*Understand when late-stage pipeline products will launch and what impact these will have on the market during the forecast period 2008 to 2017
*Quantify the current size of the seven major markets and the trends in the rest of the world
*Assess the impact of events, such as patent expiries and new product launches, on the epilepsy-specific sales of key brand name products
ABOUT DATAMONITOR HEALTHCARE 2
About the Central Nervous System pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Strategic scoping and focus 3
Datamonitor insight into the disease market 3
Related reports 5
CHAPTER 2 MARKET DEFINITION AND OVERVIEW 7
Market definition for this report 7
Countries and regions included in this report 8
Seven major market assessment 9
Seven major market dynamics 9
The seven major epilepsy market grew to almost $3.8 billion in 2007 9
Epilepsy market prescription volume has plateaued between 2004-07 10
The seven major epilepsy market is forecast to grow to over $5.5 billion by 2017 12
The UK represents the most rapidly growing epilepsy market in the seven major markets 14
Dominance of the US epilepsy market is set to continue 15
Comparison with previous forecast 19
Upgrade since 2007 forecast 19
Rest of the world snapshot 20
Rest of the world epilepsy market was almost half the size of the US market in 2007 20
The rest of Europe remains the largest region in the rest of the world 21
Turkey offers the greatest growth potential in the rest of world markets 22
Depakene (valproic acid, Abbott) is the best selling product in the rest of the world epilepsy market with 2007 sales of $190m 23
CHAPTER 3 BRAND DYNAMICS 25
Overview of competitive landscape 25
UCB's Keppra remained the market leading anticonvulsant in 2007 25
Update of key marketed anticonvulsant drugs 28
FDA acknowledgement of suicidality risk will have minimal impact on epilepsy-specific drug sales 29
Keppra (levetiracetam, UCB) 30
Cautious generic prescribing in the epilepsy market will provide Keppra with some insulation from generic erosion 31
Keppra's pediatric indication expansions look set to continue 34
Uptake in international markets will partially offset generic erosion in the US and EU 35
Topamax (topiramate, Johnson & Johnson) 36
Topamax enters Japanese epilepsy market in September 2007 37
Grant of pediatric extension will delay launch of US generics until March 2009 38
Lamictal (lamotrigine, GlaxoSmithKline) 39
Neurontin and Topamax will be Lamictal's key competitors upon launch in Japan 40
Generic lamotrigine entered the US market in July 2008 40
Depakote (valproate semisodium, Abbott Laboratories, Sanofi-Aventis) 41
Depakote has faced generic competition in the US since July 2008 41
Banzel (rufinamide, Eisai) 43
Banzel is set to enter the US epilepsy market in January 2009 44
Although well placed to penetrate the Japanese epilepsy market, Eisai is no longer expected to launch Banzel in this market 45
Lyrica (pregabalin, Pfizer) 46
Interviewed key opinion leaders do not expect Lyrica to receive strong uptake in the indication of epilepsy 47
Lyrica is expected to gain approval as monotherapy in 2011 47
Datamonitor's epilepsy-specific forecast for Lyrica has been upgraded due to greater than expected uptake during 2007 48
Sabril (vigabatrin, Sanofi-Aventis/Ovation Pharmaceuticals) 49
Sabril is expected to receive approval for the treatment of infantile spasms and refractory complex partial seizures in the US in Q1 2009 49
Despite possessing the potential to satisfy a key unmet need, approval of Sabril in the US market remains uncertain 50
Trileptal (oxcarbazepine, Novartis) 51
Generic oxcarbazepine entered the US market in October 2007 52
Frisium (clobazam, Ovation Pharmaceuticals) 53
Clinical trial data 54
Frisium will struggle to gain market share from Topamax and Banzel 56
Recently launched products 57
Stavzor (valproic acid delayed release, Noven Pharmaceuticals) 57
Clinical trial data - adjunctive use of Stavzor leads to a 45% response rate among patients with complex partial seizures 58
Stavzor will struggle to gain market share from other valproate-based medications 59
Keppra XR (levetiracetam extended release, UCB) 60
Clinical trial data: Keppra XR leads to a 46.1% median reduction of partial onset seizures 61
Keppra XR is unlikely to provide a substantial revenue boost to the Keppra franchise 62
Vimpat (lacosamide, UCB) 64
Clinical trial data - Vimpat demonstrates a lower responder rate than Keppra 65
Vimpat represents a new treatment option for patients who experience uncontrolled seizures 66
Novel, dual mechanism of action represents a key product differentiator 68
Forecasted late-stage pipeline products 70
Brivaracetam (UCB) 70
Clinical trial data 71
Retigabine (Valeant Pharmaceuticals/GlaxoSmithKline) 79
Valeant's collaboration with GlaxoSmithKline will benefit uptake of retigabine 79
Phase III data announced at two conferences in 2008: retigabine leads to a responder rate of 55.5%-38.6% 80
Revenue forecast for retigabine has been upgraded due to announcement of positive clinical trial data and Valeant's collaboration with GlaxoSmithKline 83
Carisbamate (RWJ-333369, Johnson & Johnson) 84
Carisbamate entered pre-registration in the US in October 2008 84
Low efficacy and lack of optimum switching time frame will limit uptake 85
Lamictal XR (lamotrigine extended release, GlaxoSmithKline) 90
Lamictal XR is currently experiencing regulatory delays in the US 90
An extended release version represents a small improvement to treatment options, with an unfavorable cost/benefit profile 91
Lamictal XR will play a minor role in offsetting generic erosion of Lamictal 91
Clinical trial data: Phase III data published in October 2007 91
SEP-0002093 (eslicarbazepine acetate, BIAL Group/Sepracor) 97
Future monotherapy approval and pediatric indication expansions will increase commercial potential 97
Clinical trial data 98
SPN-804 (oxcarbazepine extended release, Supernus Pharmaceuticals) 102
Clinical trial data: none available at present 103
Lack of novelty and competition from generic oxcarbazepine will limit uptake of SPN-804 104
Perampanel (Eisai) 106
Clinical trial data: Phase II results announced in April 2008 107
DP-VPA (D-Pharm) 110
Forecast downgraded due to lack of progress through development pipeline 110
Unforecasted epilepsy pipeline candidates 113
BIBLIOGRAPHY 114
Journal and conference papers 114
Websites 116
Datamonitor reports 127
APPENDIX A - MARKET ASSUMPTIONS 128
New product launches 128
Patent expiries 128
Epilepsy diagnostic values for key branded anticonvulsants 129
Standard units 129
Japanese market data 130
Derivation of sales forecasts and pricing trends 130
Sales calculations 130
Forecast methodology 131
APPENDIX B 132
Contributing experts 132
Conferences attended 132
Report methodology 132
About Datamonitor 132
About Datamonitor Healthcare 133
About the central nervous system analysis team 133
Disclaimer 135
List of Tables
Table 1: Epilepsy market sales forecasts in the seven major markets ($m), 2007-2017 17
Table 2: Comparison of leading branded drug sales ($m) for epilepsy in the seven major markets and the rest of the world (ROW), 2007 23
Table 3: Leading branded drug sales ($m) for epilepsy in the seven major markets, 2007-2017 26
Table 4: Sales forecast for late-stage R&D pipeline products for epilepsy, 2008-2017 27
Table 5: Key facts: Phase III trial of clobazam in patients with Lennox-Gastaut Syndrome 55
Table 6: Key facts: Phase III trial of brivaracetam in adults with partial onset seizures 74
Table 7: Key facts: Phase III trial of brivaracetam in adolescents and adults with epilepsy 75
Table 8: Key facts: Phase III, open-label study of a flexible dose of brivaracetam in patients aged 16 years and above 76
Table 9: Key factors impacting sales of brivaracetam, 2008-2017 77
Table 10: Clinical trial summary for retigabine IR 82
Table 11: Key factors impacting sales of retigabine IR, 2008-2017 83
Table 12: Phase III clinical trial summary for carisbamate 88
Table 13: Key factors impacting sales of carisbamate, 2008-2017 89
Table 14: Phase III clinical trial summary for Lamictal XR 93
Table 15: Key facts: Phase III trial of lamotrigine extended-release in elderly patients with epilepsy 94
Table 16: Key facts: Phase III trial of lamotrigine extended-release monotherapy for treatment of partial seizures 95
Table 17: Key factors impacting sales of Lamictal XR, 2008-2017 95
Table 18: Phase III clinical trial summary for SEP-0002093 100
Table 19: Key factors impacting sales of SEP-0002093, 2008-2017 101
Table 20: Key facts: Phase III trial of SPN-804 103
Table 21: Key factors impacting sales of SPN-804, 2008-2017 105
Table 22: Key facts: Phase III trial of perampanel 107
Table 23: Key factors impacting sales of perampanel, 2008-2017 109
Table 24: Key factors impacting sales of DP-VPA, 2008-2017 111
Table 25: Unforecasted pipeline drugs in Phase II development for epilepsy, 2008 113
Table 26: Datamonitor's estimated launch dates for epilepsy products in the seven major markets, 2008-2017 128
Table 27: Patent expiry dates for the approved anticonvulsants in the seven major markets, 2008-2017 128
Table 28: Percentage of sales attributed to epilepsy prescription for key branded anticonvulsants in the seven major markets, 2007 129
List of Figures
Figure 1: Epilepsy-specific sales value ($m) in the US, 5EU and Japan, 2004-07 9
Figure 2: Epilepsy market volume (IMS standard units sold, million) in the US, 5EU and Japan, 2004-07 10
Figure 3: Key events impacting the epilepsy market, 2008 11
Figure 4: Epilepsy-specific sales ($m) of total marketed and pipeline products in the seven major markets, 2004-2017 12
Figure 5: Key events impacting the epilepsy market, 2008-17 13
Figure 6: Epilepsy market sales value ($m) growth dynamics by country in the seven major markets, 2004-07 15
Figure 7: Epilepsy-specific sales ($m) by country in the seven major markets, 2004-2017 16
Figure 8: Comparison of depression-specific forecasts in the seven-major markets, 2006-2017 19
Figure 9: The global epilepsy market value ($m) split in by region, 2007 20
Figure 10: Epilepsy-specific annual sales of anticonvulsants in the small and emerging markets, 2004-07 21
Figure 11: Performance of the seven highest value ex-seven major epilepsy markets, 2004-07 22
Figure 12: Performance of the top six anticonvulsant brands across the seven major markets, 2004-07 25
Figure 13: Datamonitor's epilepsy-specific sales ($m) forecast for Keppra (levetiracetam) in the seven major markets, 2008-2017 35
Figure 14: Datamonitor's epilepsy-specific sales ($m) forecast for Topamax (topiramate) in the seven major markets, 2008-2017 38
Figure 15: Datamonitor's epilepsy-specific sales ($m) forecast for Lamictal (lamotrigine) in the seven major markets, 2008-2017 40
Figure 16: Datamonitor's 2007 and updated epilepsy-specific sales ($m) forecast for Depakote (valproate semisodium) in the seven major markets, 2008-2017 42
Figure 17: Datamonitor's epilepsy-specific sales ($m) forecast for Banzel (rufinamide) in the seven major markets, 2008-2017 45
Figure 18: Datamonitor's 2007 and updated epilepsy-specific sales ($m) forecast for Lyrica (pregabalin) in the seven major markets, 2008-2017 48
Figure 19: Datamonitor's epilepsy-specific sales ($m) forecast for Sabril (vigabarin)in the seven major markets, 2008-2017 51
Figure 20: Datamonitor's 2007 and updated epilepsy-specific sales ($m) forecast for Trileptal (oxcarbazepine) in the seven major markets, 2008-2017 52
Figure 21: Datamonitor's epilepsy-specific sales ($m) forecast for Frisium (clobazam) in the seven major markets, 2008-2017 56
Figure 22: Datamonitor's epilepsy-specific sales ($m) forecast for Stavzor (valproic acid delayed release) in the seven major markets, 2008-2017 60
Figure 23: Datamonitor's epilepsy-specific sales ($m) forecast for Keppra XR (levetiracetam extended release) in the seven major markets, 2008-2017 63
Figure 24: Datamonitor's sales ($m) forecast for Vimpat (lacosamide) in the seven major markets, 2008-2017 69
Figure 25: Datamonitor's epilepsy-specific sales ($m) forecast for brivaracetam in the seven major markets, 2008-2017 78
Figure 26: Datamonitor's 2006 and updated epilepsy-specific sales ($m) forecast for retigabine in the seven major markets, 2008-2017 84
Figure 27: Datamonitor's sales ($m) forecast for carisbamate in the seven major markets, 2008-2017 89
Figure 28: Datamonitor's sales ($m) forecast for Lamictal XR (lamotrigine extended release) in the seven major markets, 2008-2017 96
Figure 29: Datamonitor's epilepsy-specific sales ($m) forecast for SEP-0002093 in the seven major markets, 2008-2017 102
Figure 30: Datamonitor's epilepsy-specific sales ($m) forecast for SPN-804 in the seven major markets, 2008-2017 105
Figure 31: Datamonitor's sales ($m) forecast for perampanel in the seven major markets, 2008-2017 109
Figure 32: Datamonitor's 2006 and updated epilepsy-specific sales ($m) forecast for D-Pharm's DP-VPA in the US and 5EU, 2008-2017 112
