Report: Pipeline Insight: ADHD - Shire Driving Diversity in ADHD TOC

ABOUT DATAMONITOR HEALTHCARE

About the CNS pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis
Datamonitor insight into the ADHD market
ADHD market - key metrics
Datamonitor pipeline assessment summary

CHAPTER 2 PATIENT POTENTIAL

Disease definition and classification
Etiology of ADHD: Structural abnormalities; Genetic predisposition; Neurotransmitter dysfunction; Diagnostic criteria of ADHD; Epidemiology of ADHD
Key patient segments: Gender; Comorbidities
Clinical unmet needs of ADHD: Diagnostic complications; Hyperkinesis versus attention deficit hyperactivity disorder; Gender; Age; Duration of symptoms
Diagnostic tools: ADHD Rating Scale; Conners Rating Scale-Revised (CRS-R); Copeland symptom checklist; Barkleys Current Symptoms Scale-Self Report Form (home and school); Brown ADD Scale (diagnostic form); Parent-completed Child Behavior Checklist; Teacher Report Form (TRF) of Child Behavior Checklist; ADD-H: Comprehensive Teacher Rating Scale (ACTeRS); The IOWA Conners Rating scale
Diagnostic unmet needs

CHAPTER 3 R&D APPROACH

Classification of marketed and pipeline products: Marketed products; Stimulants - methylphenidate and amphetamines; Non-stimulants - Strattera; Pipeline compounds; Clinical trials and drug development; Regulatory barriers to the development of pediatric medications; Non-regulatory barriers to the development of pediatric medications; Novel approaches to enhance traditional pediatric clinical trials; Drug models in clinical trial development

CHAPTER 4 ADHD PIPELINE ANALYSIS

Pipeline overview: Drugs launched in 2005; Registered and Phase III overview; Phase II overview; Phase I overview; Preclinical overview; Key companies involved in the ADHD pipeline; Shire; Despite an initial decline in ADHD revenues, Shires pipeline ADHD drugs will save the day; Novartis; Focalin XR will rejuvenate Novartiss ADHD franchise, nearly doubling current revenues
Strategies for success: Innovation is key - manufacturers can no longer expect significant returns on standard extended-release formulations; Comparative positioning of pipeline drugs; Methodology of SWOT analysis

CHAPTER 5 LATE-STAGE METHYLPHENIDATE DRUG ANALYSIS & FORECASTS

Methylphenidate drugs: Recently launched drugs; Pipeline summary; Concerta - the gold-standard methylphenidate drug therapy; SWOT analysis of Concerta; Equasym XL; Equasym XL is more effective than Concerta during the morning hours; Equasym XL effective and safe in treating ADHD symptoms throughout the school day; SWOT analysis of Equasym XL; The proven safety and pharmacologic profile of Equasym XL will aid uptake in Europe; UCBs delayed launch strategy in Europe will impact long-term revenues; Equasym XL will reach peak share after the first two years of launch; Focalin XR; Focalin XR is generally perceived to act in less than one hour and remain effective for over eight hours; Focalin XR is effective in treating children and adolescents with ADHD with few adverse effects; SWOT analysis of Focalin XR; Despite the strong therapeutic profile of Focalin XR, it will face competition from numerous branded and generic extended-release stimulants in the near future; Approval for adult ADHD will significantly boost revenues; Despite the strength of Focalin XRs therapeutic profile and marketing potential, it will be hindered by generic stimulants and novel ADHD drugs; MTS; MTS; MTS failed to demonstrate clinical significance on the primary endpoint in its first Phase III clinical trial; MTS is significantly superior to placebo, with significantly improved scores in teacher, parent and clinician ratings of patient behavior and attention; MTS demonstrates significant efficacy compared to placebo in Phase II classroom study; MTS demonstrates significant efficacy compared to placebo in Phase II classroom study; SWOT analysis of MTS; Kids will love MTS; Patch technology improves safety, compliance and duration of action; MTS will become the market-leading stimulant by 2010

CHAPTER 6 LATE-STAGE AMPHETAMINE DRUG ANALYSIS & FORECASTS

Amphetamine drugs: Pipeline summary; Adderall XR - the gold-standard amphetamine drug therapy; SWOT analysis of Adderall XR; NRP-104; NRP-104 achieves similar blood amphetamine levels to current extended-release amphetamine products; NRP-104 demonstrates comparable efficacy to Adderall XR; SWOT analysis of NRP-104; NRP-104 - the first non-scheduled stimulant; Equivalent efficacy to Adderall XR in treating children and adults; NRP-104 will become the market-leading amphetamine by 2010; SPD-465; SWOT analysis of SPD-465; SPD-465 may sustain effect for too long in pediatric patients, limiting uptake; With Shires already strong ADHD pipeline, what will be the fate of SPD-465?; SPD-465 will be overshadowed by NRP-104

CHAPTER 7 LATE-STAGE OTHER ADHD DRUG ANALYSIS & FORECASTS

Other ADHD drugs: Pipeline summary; Strattera - the gold-standard non-stimulant drug therapy; SWOT analysis of Strattera; Attenace (modafinil); Attenace consistently exhibits a robust efficacy on both the inattentive and hyperactive symptoms of ADHD; Attenace significantly improves ADHD symptoms and is well tolerated in children with ADHD; Attenace improves ADHD symptoms in children; Attenace improves cognition and response inhibition in adult ADHD; SWOT analysis of Attenace; Attenace (modafinil) will be well received as it is an established schedule IV drug with a proven safety record, approved across the seven major markets; Attenace to target comorbid cognitive deficits in ADHD; Attenace will climb to fourth position in the ADHD market by 2012; SPD-503; Guanfacine in the treatment of adult ADHD; Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders; Increased prescribing of guanfacine, in the absence of severe side effects; Guanfacine is a safe and effective treatment for children with tic disorders and ADHD; Ongoing Phase III pivitol studies; SWOT analysis of SPD-503; SPD-503 will have little time to maximize revenues before genericization; CX-516 & CX-717 (AMPAKINE); SWOT analysis of AMPAKINES; AMPAKINES - a additive cognitive enhancer to traditional ADHD therapy; SGS-742; SWOT analysis of SGS-742; The first drug to solely target adult ADHD
Late-stage development compounds recently discontinued: TC-5231 (mecamylamine oral gel capsules); SPD473; NS-2359; ABT-089

CHAPTER 8 INNOVATIVE EARLY-STAGE PROJECTS

Innovative early-stage projects: SON-216 (bifemelane); DOV-102677; Dextroamphetamine (transdermal patch); Lobeline; DAR-0300; PGI-256 and PGI-415; SPD-483

APPENDIX A

ADHD market data
KOL interviews
Contributing experts
Bibliography

APPENDIX B

Report methodology
About Datamonitor

List of Tables

Table 1: Forecast revenues of pipeline ADHD drugs to 2015 across the seven major markets
Table 2: Summary of ADHD pipeline drug SWOT analysis and peak US market share
Table 3: Symptoms for ADHD/HKD in the DSM-IV and ICD-10
Table 4: Definition of ADHD in the DSM-IV
Table 5: Prevalence of ADHD
Table 6: Prevalence, diagnosis and drug treatment rates of patients with ADHD across the seven major markets
Table 7: Forecast prevalence (000s) of ADHD across the seven major markets to 2010
Table 8: ADHD drugs in launched in 2005
Table 9: ADHD drugs in pre-registration, 2005
Table 10: ADHD drugs in Phase III clinical development, 2005
Table 11: ADHD drugs in Phase II clinical development, 2005
Table 12: ADHD drugs in preclinical development, 2005
Table 13: Revenues ($m) from Shires marketed CNS drugs across the seven major markets, (2001-04)
Table 14: Shires marketed and pipeline ADHD drugs, 2005
Table 15: Revenues ($m) from Novartiss marketed CNS drugs across the seven major markets, 2001-04
Table 16: Novartiss marketed and pipeline ADHD drugs, 2005
Table 17: Opportunity/threat factors and weightings
Table 18: Opportunity/threat factors - scoring definitions
Table 19: Strength/weakness factors and weightings
Table 20: Strength/weakness factors - scoring definitions
Table 21: Methylphenidate drugs in launched in 2005 to date
Table 22: Methylphenidate drugs in late stage development, 2005
Table 23: SWOT analysis of Concerta
Table 24: SWOT analysis of Equasym XL
Table 25: Forecast revenues of Metadate CD/Equasym XL across the seven major markets to 2015
Table 26: SWOT analysis of Focalin XR
Table 27: Promotional spend vs. drug revenues in the first year after launch
Table 28: Forecast revenues of Focalin XR across the seven major markets
Table 29: SWOT analysis of MTS
Table 30: Forecast revenues of MTS across the seven major markets
Table 31: Amphetamine drugs in late stage development, 2005
Table 32: SWOT analysis of Adderall XR
Table 33: SWOT analysis of NRP-104
Table 34: Forecast revenues of NRP-104 across the seven major markets
Table 35: SWOT analysis of SPD-465
Table 36: Forecast revenues of SPD-465 across the seven major markets
Table 37: Other ADHD drugs in late stage development, 2005
Table 38: SWOT analysis of Strattera
Table 39: SWOT analysis of Attenace
Table 40: Forecast revenues of Attenace across the seven major markets
Table 41: SWOT analysis of SPD-503
Table 42: Forecast revenues of SPD-503 across the seven major markets
Table 43: SWOT analysis of AMPAKINES
Table 44: SWOT analysis of SGS-742
Table 45: ADHD drugs recently suspended or discontinued, 2005
Table 46: ADHD drugs in preclinical development, 2005
Table 47: Strattera key facts
Table 48: Key Strattera events, 2003-2005
Table 49: Adderall and Adderall XR key facts
Table 50: Key Adderall and Adderall XR events, 2003-2005
Table 51: Concerta key facts
Table 52: Key Concerta events, 2003-2005
Table 53: Metadate franchise key facts
Table 54: Key Metadate franchise events, 2003-2005
Table 55: ADHD drugs in pre-clinical development, 2005

List of Figures

Figure 1: SWOT analysis of ADHD pipeline drugs compared to the gold standards marketed comparator products
Figure 2: Key findings from the UK ADDIS ADHD study
Figure 3: NICE method for measuring cost-effectiveness of drug treatment for ADHD
Figure 4: US sales of Shires Adderall ADHD franchise and its generic competitors
Figure 5: US revenue forecast of Shires ADHD franchise to 2015
Figure 6: SWOT analysis of Shires ADHD franchise
Figure 7: US revenues of Novartiss ADHD franchise
Figure 8: US revenue forecast of Novartis ADHD franchise to 2015.
Figure 9: SWOT of Novartiss ADHD pipeline
Figure 10: US revenues of stimulants (schedule II, and schedule II or non-classified) and non-stimulants to 2015
Figure 11: SWOT analysis of ADHD pipeline drugs compared to the gold-standard marketed comparator products
Figure 12: SWOT analysis of methylphenidate ADHD pipeline drugs compared to the gold standard-Concerta
Figure 13: Pharmacologic profile of Equasym XL compared to Concerta
Figure 14: Pharmacologic profile of Focalin XR compared to Concerta
Figure 15: Pharmacologic profile of MTS compared to Concerta
Figure 16: SWOT analysis of amphetamine ADHD pipeline drugs compared to the gold standard-Adderall XR
Figure 17: Pharmacokinetic profile of NRP-104 compared to marketed extended-release amphetamines
Figure 18: NRP-104 efficacy and duration of action - time course of SKAMP (least mean squares S.E.)
Figure 19: Pharmacologic profile of NRP-104 compared to Adderall XR
Figure 20: Pharmacologic profile of SPD-465 compared to Adderall XR
Figure 21: SWOT analysis of other ADHD pipeline drugs compared to the gold standard-Strattera
Figure 22: Pharmacologic profile of Attenace compared to Strattera
Figure 23: Change from baseline in ADHD-RS
Figure 24: Pharmacologic profile of SPD-503 compared to Strattera
Figure 25: Pharmacologic profile of AMPAKINES compared to Strattera
Figure 26: Pharmacologic profile of SGS-742 compared to Strattera