cowen and company 32nd annual healthcare...
TRANSCRIPT
Our purposeWe enable people with life-altering conditions to lead better lives.
Cowen and Company 32nd
Annual Healthcare Conference
Shire plc
Dr. Jeffrey JonasSVP, R&D, Specialty Pharmaceuticals and Regenerative Medicine
To be as brave as the people we help.
2
THE “SAFE HARBOR”
STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company’s Specialty Pharmaceuticals, Human Genetic Therapies and Regenerative Medicine products, as well as the ability to secure new products
for commercialization and/or development; government regulation of the Company’s products; the Company’s ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company’s products; the Company’s ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company’s ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company’s filings with the Securities and Exchange Commission.
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Human Genetic Therapies (HGT)Orphan Diseases
Specialty Pharmaceuticals (SP)Attention Deficit Hyperactivity Disorder (ADHD) ,
Gastrointestinal (GI), Renal, Hematology
Advanced BioHealing
(ABH)Regenerative Medicine
Acquisition of ABH adds a strategic platform in Regenerative Medicine
Shire’s balanced product portfolio continues to drive good earnings growth
To be as brave as the people we help.
4
KEY
PRODUCTS
LATE STAGE PIPELINE
EARLY STAGE PIPELINE
VALIDATING TECHNOLOGY PLATFORMS
RESOLOR
LIALDA
VYVANSE
ELAPRASE
REPLAGAL
VPRIV
INTUNIV
FIRAZYR
DERMA-
GRAFTREPLAGAL US
Investing to deliver growth now and into the future, supported by strong cash generation
LIALDA DVVYVANSE
MDD
Regen
Medassets
VYVANSEEx-US
Specialty PharmaVyvanse New Uses
CarrierwaveHematology
Movetis
assets
HGT Hunter CNSSanfilippo ASanfilippo B
DMDMLD
Emer
ging
Res
earc
h A
sset
s
INTUNIVEx-US
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5
8,467,008
6,987,453
0
1,000,000
2,000,000
3,000,000
4,000,000
5,000,000
6,000,000
7,000,000
8,000,000
9,000,000
TRx
Vyvanse
21.2% Growth
20102011
Source: IMS NPA Monthly
VYVANSE TRx
growth outpaced ADHD market growth (10.4%) in 2011
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VYVANSE ADHD Life Cycle Management Objectives
•
Differentiation
–
to help physicians and patients make better decisions about treatment while delivering value to payors
and policymakers
•
Evolution
–
to provide a stream of new information to support promotional efforts and strengthen positioning
•
Science
–
to advance understanding of the disorder
•
Globalization
–
to leverage our experience in the US as we prepare to launch in the EU
Our purposeWe enable people with life-altering conditions to lead better lives.
VYVANSE®
Maintenance Treatment in Adults with ADHD
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More Than 90% of Patients Taking VYVANSE Continued to Maintain Symptom Control vs
25% of Patients Taking Placebo
Our purposeWe enable people with life-altering conditions to lead better lives.
VENVANSE®
(VYVANSE®) EUOverview of Study 325 Data
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VENVANSE (VYVANSE) EU
•
Filed in the EU Dec 2011
•
Opportunity to grow market and treatment rates
•
Ph 3 Study SPD489-325 (including methylphenidate as a reference arm) •
Double blinded placebo and active-controlled study in children and adolescents aged 6-17 with ADHD
•
Conducted at 48 sites across Europe; approximately 200 patients completed trial
•
Showed that Vyvanse demonstrated robust efficacy on all key endpoints •
Safety profile consistent with the known effects of amphetamine treatment and previous Vyvanse trials
•
Ph 3 Study 317 (including Strattera
comparator): ongoing
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-5.7
-18.7*-24*-30
-20
-10
0
10
20
30
40
50
Baseline Endpoint LS Mean Change From Baseline
AD
HD
-RS
Mea
n To
tal S
core
*P<0.001FAS=full analysis set (n=332)
Placebo SPD489
(VYVANSE EU)
Concerta
SPD489-325 Mean Change
from
Baseline
in
ADHD-RS-IV
Total
Score
Our purposeWe enable people with life-altering conditions to lead better lives.
Effectiveness of VYVANSE®
Compared to Concerta
in Adolescents With ADHD
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Strategic rationale for trial of VYVANSE versus Concerta
•
As a leader in ADHD therapy and research, Shire is committed to
expanding our knowledge about ADHD and its treatment. This, first-of-its-kind, head-to-head trial is an example of this commitment.
•
It is incumbent upon us to continue to demonstrate the clinical
value of our products in a data-driven manner that is backed by rigorous clinical science.
•
Based on our data from the 325 study where Concerta
was a reference arm, new trials have a good probability of differentiating VYVANSE from Concerta
in ways that will be clinically meaningful to patients, physicians, and payors
• Study design•
2 studies, 6-8 weeks, use of ADHD-RS-IV and CGI-I scales, multiple doses, US sites•
Approximately 1000 patients to be studied•
Completed by 2H 2013
Our purposeWe enable people with life-altering conditions to lead better lives.
VYVANSE®
New Uses Update
This communication describes investigational studies which evaluate the potential use of VYVANSE in treating non-ADHD conditions. These data are presented to inform the medical and financial communities about Shire development programs. No conclusions can be drawn regarding the safety or efficacy of VYVANSE in any of these other conditions without additional studies and review by regulatory authorities. VYVANSE is approved only for the treatment of Attention Deficit Hyperactivity Disorder. Shire does not recommend the use of its products in any way other than as described in the Prescribing Information.
Our purposeWe enable people with life-altering conditions to lead better lives.
VYVANSE®
New Uses Update
Investigation of dopamine-norepinephrine modulation in
Major Depressive Disorder (MDD)
Excessive Daytime Sleepiness (EDS)
Negative Symptoms in Schizophrenia (NSS)
Binge Eating Disorder (BED)
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17Kessler RC et al. Am J Psychiatry 2006;163:716-723; Atlfas
et al. BMC Psychiatry 2002;2:9; Hudson et al. Biol Psychiatry 2007;61:348-358; Ross et al. Schiz. Res 2006;88:90-
95; Wingo
et al. J Clin Psychiatry, 2007, 68:11:1776-1784; Walters et. al. J Clin Sleep Med, 2008, 4:6:591-600; Dunlop & Nemeroff Arch Gen Psych (2007); 64:327-37.
As VYVANSE impacts DA and NE transmission, therapeutic effects may be seen in symptomatic disorders involving these neural pathways
Dopamine Norepinephrine
MOOD
COGNITION
INTEREST
INHIBITION
ENERGY
MOTIVATION
WAKEFULNESS
ADHD
Major Depression
Excessive Daytime Sleepiness
Schizophrenia
Binge Eating
VYVANSE NEW USES
Dopamine (DA) and norepinephrine (NE) dysregulation is implicated in many neuropsychiatric disorders
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VYVANSE New Uses
Dopamine modulation in reward systems across CNS disorders
‘Reward’
thermostatmediates the internal response to
motivational stimuli
Motivational stimuli include food, water, drugs of abuse,
social interaction, emotional experience
Reward tone can be over and under set
(risk judgment, attention imbalance, anhedonia [joy], avolition [will])
Disordered dopamine tone in substance abuse, ADHD, depression, schizophrenia, eating disorders, modulating this tone may produce clinical benefit
Salamone JD et al. Curr Opin Pharm 2004: 5(1); 34-41; Bressan & Crippa. Acta Psych Scand 2005:111(s427);14-21; Martin-Soelch C. Biochem Soc Trans 2009:37;313-7; Volkow ND et al. JAMA 2010: 302(10);1084-91. Buckholtz JW et al. Nature Neurosci 2010:13; 419-21; Wang GJ et al. Obesity 2011;19:1601-8
DopamineDopaminetonetone
Dopamine chemically modulates the level of reward perceived
NORMAL
HighLow Rewardperception
Less reward
Our purposeWe enable people with life-altering conditions to lead better lives.
VYVANSE® Major Depressive Disorder
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VYVANSE NEW USES
Augmentation of first-line anti-depressants for inadequately responsive MDD
•
Placebo-controlled Phase 2 trial in ‘all comers’
showed clinically meaningful improvement in depressive symptoms (MADRS) and disability (SDS)
•
‘All comers’
reflects all patients, regardless of which residual symptoms are prominent (e.g., sadness, anxiety, energy, concentration)
•
Additional Phase 2 trial in MDD patients near or at remission
with persistent cognitive impairment using patient-centric approach
•
Approximately 20 to 30% of MDD patients have persistent cognitive problems despite improvement in core depressive symptoms
•
Exploring potential innovative pathway for development and pharmacoeconomic
benefit in targeted patients, given the disability associated with persistent cognitive impairment
•
Phase 3 program enrolling globally: 3 controlled, short-term trials and 1 open-label long-term trial
•
Enrollment ~ 24 months, Treatment: 4 to 12 months, depending on trial•
Final submission expected to include ~1,500 subjects
MADRS=Montgomery-Åsberg Depression Rating Scale; SDS=Sheehan Disability Scale; Iverson et al, J Aff Disord (2011); Hasselbalch et al, J Aff Disord (2010): 134 (1-2): 20-31.
Our purposeWe enable people with life-altering conditions to lead better lives.
VYVANSE® Negative Symptoms of Schizophrenia
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VYVANSE NEW USES (NSS)
Market Dynamics
Diagnosis rate = 95%
Treatment rate = 73%
Negative Symptoms = 65%
CAGR [2008-2018] of each rate = 1.04%
Prevalence of Schizophrenia
6,645,156
Prevalence of Schizophrenia
6,645,156 Diagnosed6,312,899
Diagnosed6,312,899 Treated
4,608,416Treated
4,608,416 Negative Symptom Patients
2,995,470
Negative Symptom Patients2,995,470
WHO report, global burden of Disease 2004 (2008), www.who.int, Decision Resources Schizophrenia Report 1/2010, Sartorius N, Schiz. Bulletin: 21-34,1974;Knapp et al., Schiz. Bulletin (30), 2, p279-293, 2004; Wu et al, J Clin
Psych 2005; Sources: Eurostatand
US Census, Commercial Insight: Antipsychotics, October 2009; Decision Resources Shire Estimates
3.0 million candidates for treatment (G7 in 2010)
Estimated Total Societal Cost (G7)
~ $120 Billion per year
Estimated Total Societal Cost (G7)
~ $120 Billion per year
Total Atypical Antipsychotic Market Value (2008)$18.2 Billion per year
Total Atypical Antipsychotic Market Value (2008)$18.2 Billion per year
Potential NSS Market Value
>$1 Billion
Potential NSS Market Value
>$1 Billion
•
Lifetime disability•
Multiple hospitalizations•
Dependence on public careMedication
Costs
•
No consensus of approved medication or medications for NSS
Schizophrenia presents substantial societal costs to offset (G7)
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VYVANSE NEW USES (NSS) –
study design
3 week screening
(no VYVANSE)10 week open label
( augmentation with VYVANSE of atypical antipsychotics)4 week double blind,
randomised discontinuation
•
Patients stable on atypical antipsychotic medication
•
Stability confirmed over three weeks
•
No depression (CDSS ≤
9)
•
No EPS
•
Mild positive symptoms
•
10 week open label VYVANSE augmentation of atypical antipsychotics
•
92 enrolled, 69 completed
•
Weekly BLINDED assessments
•
Optimised dose over 20 to 70 mg/d range
•
4 week double blind discontinuation
•
35 patients switched to placebo
•
34 patients continued VYVANSE
•
Weekly BLINDED assessments
•
Study 204: A blinded rater
open-label, double blind withdrawal design•
21 sites, mean age = 42, average dose = 52mg•
Entry into open label required SANS Total ≥
55, CDSS ≤
9, SAS Akinesia
<2, and PANSS Positive subscore
< 20
Efficacy Measurements•
Negative symptoms (1º
endpoint)•
Positive symptoms•
Psychiatric symptoms, depression-anxiety•
Global Clinical Assessments•
Cognitive functioning•
Real-world functioning
Safety Measurements•
Movement disorder symptoms•
Suicidal thinking•
Amphetamine cessation symptoms•
Sleep quality •
Vital Signs, Adverse Events•
Fasting laboratories, ECG
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VYVANSE NEW USES (NSS) -
Safety
No new issues in population expected to experience tolerability issues
Disposition•
All cause discontinuation: 25% in OL, 14% in DB (no group differences)•
Most common: ‘withdrawal by subject’
(12 –14%)•
Adverse event discontinuations: 5.4% in OL, 2.2% in DB
Treatment-emergent adverse events (≥
5%)•
Headache
14.1%•
Insomnia
10.9%•
Decreased Appetite
10.9% •
Dizziness
8.7%•
Dry Mouth
6.5% •
Diarrhea
5.4% •
Across both phases, ‘exacerbation of illness’
in 3.2% of subjects receiving Vyvanse and 1.1% of subjects receiving placebo
Vital Sign mean changes (Week 10)•
Systolic BP (mmHg)
2.6 Diastolic BP (mmHg) 2.5•
Pulse (bpm) 5.1 Weight (kg) -0.46 No clinically significant changes in laboratories or ECG measurements
Data Source SPD489-204: Tables 4.2.2.1; 4.2.2.3; 4.6.6.1; 4.7.2 15-Mar-2011; Shire data on file
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25Data Source SPD489-204: Tables 3.1.1.1, 3.1.2.4, 15-Mar-2011; Shire data on file
VYVANSE NEW USES (NSS) –
Clinical Effect on Negative Symptoms
Improvement in open-label, no rebound in randomized discontinuation
40
45
50
55
60
65
-3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 10 11 12 13 14Week
SANS-18TOTAL SCORE
ScreeningNo VYVANSE
OL Augmentationof Atypical Antipsychotics
DB RandomizedDiscontinuation
**VYVANSE n= 35
Placebo n= 34
Enrolled n= 92
Completed n= 69
Of Week 10 completers, 52.9% of subjects categorized as responders (≥
20% improvement from Week 0)
No significant difference between PBO and VYVANSE
at Week 14
Low
er R
efle
cts
Impr
ovem
ent
**p<0.0001 compared to baseline (LOCF)**p<0.0001 compared to baseline (LOCF)
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VYVANSE NEW USES (NSS) –
Clinical Effect on Positive Symptoms
Mean PANSS Total and subscale scores
Data Source SPD489-204: Tables 3.2.4.1 to 10, 15-Mar-2011; Shire data on file
10
15
20
25
30
35
40
-3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 10 11 12 13 14Week
**
**
PANSSSUB-
SCALESCORES
PANSS Negative Score mean (7-items)
PANSS Positive Score mean (7-items)
PANSS General Psychopathology Score mean (14-items)
VYVANSE n= 35
Placebo n= 34
VYVANSE n= 35
Placebo n= 34
VYVANSE n= 35
Placebo n= 34
10 11 12 13 14Week
Decrease in general (non-
psychotic) symptoms
Decrease in negative
symptoms
No increase in positive
symptoms
No significant difference between PBO and VYVANSE at Week 14
In the OL phase, mean PANSS Total Score decreased from 73.8 (Week 0) to 63.9 (Week 10), or
-9.8 points** (95% CI: -11.7 to -8.0)
Low
er R
efle
cts
Impr
ovem
ent
**p<0.0001 compared to baseline (LOCF)**p<0.0001 compared to baseline (LOCF)
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VYVANSE NEW USES
Summary and Next Steps for VYVANSE in NSS
Summary
•
Improvement with VYVANSE augmentation during OL-blinded rater phase; no worsening/rebound during short DB phase
•
Slow/little offset of activity over 4 weeks suggests conventional withdrawal designs may suffice
•
No new or unexpected safety findings across psychiatric (positive symptoms, anxiety, depression) and medical (laboratories, vital sign, ECG) parameters
•
Negative symptom improvements supported by collateral improvements in other clinical domains
•
Positive health authority and global thought leader response to current data set
Next Steps
•
Establish potential/parameters for biomarkers for response, including commercially viable diagnostic and maintenance tools
•
Given tolerability in previous trial (highest VYVANSE doses), exploring risk-benefit profile of a higher dose range prior to initiating Phase 3 to enable optimal clinical use
•
Potential to initiate Phase 3 by end 2012
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Indication Status
Excessive Daytime Sleepiness •
Completing health authority interactions regarding potential for comparative labeling to enable optimal commercial positioning
Binge Eating Disorder •
Phase 2 trial enrollment completed•
Expected data availability mid-year 2012
VYVANSE –
Other New Use Programs
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2012 Key newsflow
Lexington manufacturing plant US approval for VPRIVLexington manufacturing plant US approval for VPRIV
Potential REPLAGAL US approvalPotential REPLAGAL US approval
LIALDA diverticular
disease Phase 3 dataLIALDA diverticular
disease Phase 3 data
VYVANSE binge eating disorder Phase 2 dataVYVANSE binge eating disorder Phase 2 data
Potential DERMAGRAFT Canadian approvalPotential DERMAGRAFT Canadian approval
Potential VENVANSE EU approvalPotential VENVANSE EU approval
Sanfilippo A and Hunter Intrathecal
program updatesSanfilippo A and Hunter Intrathecal
program updates
Specialty Pharma Human Genetic Therapies Regenerative Medicine
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Consistent strategy continues to deliver
Balanced product portfolio expected to continue to deliver good earnings growth
Balanced product portfolio expected to continue to deliver good earnings growth
Delivering valuable and innovative treatments to meet the changing healthcare environment
Delivering valuable and innovative treatments to meet the changing healthcare environment
Investing in promising mid and late stage pipeline opportunities
Investing in promising mid and late stage pipeline opportunities
Our purposeWe enable people with life-altering conditions to lead better lives.
Questions and Answers Breakout Room –
Wellesley, 3rd
floor
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Pipeline (at February 9, 2012)
SPD 535Platelet Reducing
VENVANSE (EU)
ADHD
SPD 557 (M0003)rGERD
VYVANSEMDD
Guanfacine
Carrier WaveDERMAGRAFT
(Canada) DFU
HGT 1410 Sanfilippo A(1)
HGT 2310Hunter CNS(1)
HGT 4510
DMD(2)
HGT 1110 MLD
Phase 1 Preclinical and Discovery Phase 2 Phase 3 Registration
XAGRID (Japan)
Essential Thrombocythaemia
LIALDA
Diverticular
Disease
INTUNIV (EU) ADHD
VYVANSE
NSS/EDS/BED
ADHD/CNSGIHematologyRegenerative Medicine
ERTDMDNew projectsProject advancement
INTUNIV (Canada) ADHD
REPLAGAL (US) Fabry Disease
HGT 3010 Sanfilippo B
RESOLOR (US)
Chronic Constipation (3)
Changes to the pipeline since third quarter 2011Progress•VENVANSE (EU) in ADHD moved from phase 3 to registrationAdditions •Addition of HGT 3010 Sanfilippo B in preclinical•RESOLOR US added post Shire’s acquisition of rights in the USDiscontinued•Carrier Wave for Pain –
phase 1•SPD 556 (M0002) Ascites
–
phase 2
Note(1)
HGT 1410 and HGT 2310 are currently in Phase 1/2 clinical trials(2)
Currently on clinical hold(3)
Phase 3 ready
Early Research
To be as brave as the people we help.
34Source: IMS NPA Monthly
2011 ADHD market growth primarily driven by Adults
27,499,681
25,689,195
25,553,271
22,642,946
‐
10,000,000
20,000,000
30,000,000
40,000,000
50,000,000
60,000,000
TRx
2011 2010
Ped (6‐17) Adult (18+)
Ped7.6% Growth
2011
Adult13.5% Growth
2011
Overall ADHD Market Growth 10.4%