Karl Mahler, Head of Investor Relations Eugene Tierney, Global Product Strategy TA Head, CNS - Translating excellence in science into customer ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Translating excellence in science into customer benefit – an update on CNS portfolio Karl Mahler, Head of Investor Relations Eugene Tierney, Global Product Strategy TA Head, CNS
Performance update and strategy
Update on CNS portfolio
2
Q1 2011: Group sales
Supporting full-year guidance, strong currency impact
2010 2011 change in % Excluding
CHF m CHF m CHF local Tamiflu1
Pharmaceuticals Division 9,727 8,712 -10 -2 +1
Diagnostics Division 2,518 2,408 -4 +6 +6
Roche Group 12,245 11,120 -9 0 +2
3
1 local currency
Roche: Focused on medically differentiated
therapies
Focus Pharma Dia
Premium for innovation
MedTech
OTC
Generics
Differentiation
4
Key Pharmaceuticals & Diagnostics products
A risk-diversified portfolio of drugs and BUs
35 2 with > than CHF 6 bn
1 with > than CHF 5 bn
Avastin
>CHF 6bn*
30 11 with > than CHF 1 bn
25 MabThera/Rituxan
Sales (CHF bn)
>CHF 5bn*
20
Herceptin
15 Diabetes Care
Pegasys
Immunochemistry
CellCept
>CHF 1bn*
10
NeoRecormon
Tarceva
Clinical Chemistry
5 Xeloda
Lucentis
Molecular Dx
0 Boniva
'03 '04 '05 '06 '07 '08 '09 '10 5
* 2010 sales
Roche: Limited exposure to patent expiries in
the short and medium term
2010 2011 2012 2013
40%
35%
30%
25%
Business impact
20%
from biosimilars 2014/15
15% and beyond?
10%
5%
0%
% Sales Lost calculated by subtracting given year sales (‘10, ’11, ‘12, ‘13) from full year sales from year prior to LOE.
Data excludes sales lost impact of products with LOE prior to 2010. 6
Source: Evaluate Pharma
Long patent protection
Biosimilars facing high hurdles
Long primary patent Biosimilars outlook
protection of our key
biologics
EU US: recent healthcare legislation
Patents US opens pathway for biosimilars
ROW/EM
Avastin 2019 similar FDA in the process of developing
guidelines
marketed
Lucentis 2019
by Novartis Data exclusivity for biologics 12 years
Rituxan/
2018 earlier EU: legal and regulatory hurdles likely
MabThera
to remain high for biosimilars
Herceptin 2019 earlier
Pegasys 2018 similar ROW/EM: investment in countries
with strong IP regulations (China)
Brand awareness important
7
A leading pipeline
12 NMEs in late-stage development
Number of NMEs
Virology
CNS 12
HCV pol inh1
Metabolic
10 ocrelizumab MS
Inflammation Glycine Glycine
reuptake inh reuptake inh
Oncology aleglitazar aleglitazar
taspoglutide dalcetrapib
dalcetrapib lebrikizumab1
ocrelizumab MetMAb1
4 Hedgehog inh Hedgehog inh
taspoglutide BRAF inhibitor BRAF inhibitor
2 dalcetrapib T-DM1 T-DM1
GA101
ocrelizumab ocrelizumab GA101 (CLL)
(CLL, NHL)
Actemra pertuzumab pertuzumab pertuzumab
2007 2008 2009 2010
8
1 LIP decision made, phase III start pending
Creating medical value and improving patient care
Six NMEs in late-stage development have PHC approach
Diagnostics
HER2/3 Met Periostin
(Pertuzumab) (MetMAb) (lebrikizumab)
Companion
Diagnostics HER2 BRAF V600 HCV load, genotype
(T-DM1) (BRAF inh) (HCV pol inh)
NMEs = new molecular entities PHC = Personalised Healthcare 9
Not all products available in all countries; some products in development
We need to stay above industry success rates
Roche
2008 2009 2010 2011 (Jan-Mar)
Success (+)
Failure (-) (+) (-) (+) (-) (+) (-) (+) (-)
Phase II 6 6 7 1
Phase III 21 2 20 1 10 6 4 0
Total 27 2 26 1 17 6 5 0
Ph III success rate 91% 95% 62% 100%
Industry ph III
success rate
63%1 64%2
10
Based on IR up-dates KMR Group, 1)= 2006-2008, 2)= 2007- 2009,Key clinical trials since October 2010
18 positive studies in 6 months
Compound Indication Study
MetMAb 2nd/3rd line NSCLC Randomised Phase II, ESMO 2010
Avastin front line Ovarian Cancer ICON7 Phase III, ESMO 2010
Ocrelizumab RR Multiple Sclerosis Randomised Phase II, ECTRIMS 2010
Mericitabine (RG7128) Hepatitis C PROPEL randomised Phase IIb, interim data AASLD 2010
Vemurafenib (BRAF inh) Metastatic Melanoma BRIM2 Phase II, Melanoma Research Congress 2010
GA101 Non-Hodgkin's Lymphoma Randomised Phase II, ASH 2010
Glycine Reuptake inh. (GlyT-1) Schizophrenia Randomised Phase II, ACNP 2010
Pertuzumab Neoadjuvant HER2+ Breast Cancer NEOSPHERE randomised Phase II, SABCS 2010
Lebrikizumab Asthma Randomised Phase II, data in house
Dalcetrapib CV risk reduction Dal-VESSEL, Dal-PLAQUE safety data in house
T-DM1 1st line HER2-positive breast cancer Randomised Phase II, Apr 2011
Vemurafenib (BRAF inh) Metastatic Melanoma BRIM3 Phase III interim analysis, Jan 2011
Tarceva Advanced NSCLC EURTAC Phase III interim analysis, Jan 2011
Avastin Relapsed Ovarian Cancer OCEANS Phase III, Feb 2011
Lucentis Diabetic macular edema (DME) RISE and RIDE, 2 Phase III studies, Feb-Mar 2011
Vismodegib (Hedgehog inh) Basal Cell Carcinoma (mBCC) Pivotal Phase II, Mar 2011
11
Pivotal studies in Q1 2011Performance update and strategy
Update on CNS portfolio
12The burden of brain disorders is one of the
greatest challenges facing society today…
Cause YLD* Cause Percent of
millions total
DALYs*
1 Unipolar depression 41.0
1 Unipolar depression 8.2
2 Refractive errors 14.0
2 Ischemic heart disease 6.3
3 Hearing loss, adult onset 13.3
3 Cerebrovascular disease 3.9
4 Cataracts 9.9
4 Alzheimer & other dementias 3.6
5 Osteoarthritis 9.5
5 Alcohol use disorders 3.4
6 Schizophrenia 8.0
6 Hearing loss, adult onset 3.4
7 Anaemia 7.4
7 COPD 3.0
8 Bipolar Disorder 7.1
8 Diabetes mellitus 3.0
9 Birth asphyxia & birth 6.9
trauma 9 Trachea, bronchus, lung 3.0
cancers
10 Alzheimer & other dementia 5.8
10 Road traffic accidents 2.6
*YLD: Years lived with disability
*DALYs: Years of life lost due to death and disability
13 WHO’s Global Burden of Disease Report, 2004… and yet commitment to the field is wavering
AstraZeneca drops psychiatric, other drug research
The decision to drop psychiatry drug research reflects the
unpredictable and risky nature of clinical trials to assess medicines
working on the brain, as well as a lack of good scientific opportunities,
development head Anders Ekblom told Reuters.
LONDON, March 02, 2010 (Reuters)
Glaxo to Close Italy R&D Center
Feb. 5 -- GlaxoSmithKline Plc, the U.K.’s biggest drugmaker, plans to
close a facility in Verona, Italy, affecting more than 500 research jobs,
labor unions said.
Glaxo’s northern Italian center, which specializes in neuroscience
research, will be closed by the end of this year, the Filcem-Cgil, Femca-
Cisl and Uilcem-Uil unions said in a joint e-mailed statement last night.
February 05, 2010 (Bloomberg)
14Emerging knowledge of neurobiology opens new opportunities Vision Roche Neuroscience harnesses emerging science for serious patient needs Strategy • Focus on serious conditions with no approved, effective or safe treatments • Deliver a differentiated portfolio by focusing on mechanism-based drug discovery • Optimize benefit through early intervention and personalized treatment • Understand the needs of stakeholders: patients, prescribers, regulators & payors Therapeutic areas of focus • Schizophrenia (negative and persistent symptoms) • Depression (Treatment-Resistant Depression) • Neurodevelopmental disorders (Fragile X, Down’s, Autism) • Neurodegeneration (Alzheimer’s Disease, Parkinson’s Disease, Multiple Sclerosis) 15
Glycine reuptake inhibitor (GlyT-1) RG1678, the first GRI in schizophrenia
Schizophrenia
Disease and epidemiology
Multiple symptoms
Epidemiology*
POSITIVE
• Hallucinations Country Diagnosed
• Delusions Prevalence
• Thought disorder (%)
• Bizarre behavior US 0.7
Japan 0.8
NEGATIVE MOOD France 0.7
• Anhedonia • Anxiety Germany 0.8
• Social withdrawal • Depression
• Self-neglect Italy 0.8
Spain 0.7
UK 0.8
COGNITIVE
• Attention deficits
• Poor executive function
• Poor working
memory
17
* Source: Decision Resources, Jan. 2010Available treatment options
Only positive symptoms addressed by antipsychotics
Positive
Dual-dopamine/5HT2 antagonists:
• Poor efficacy in negative and cognitive
symptoms
• Low tolerability: EPS (movement disorders),
hypotension, obesity, diabetes, QTc
prolongations Mood
Anti-depressants
Negative Mood stabilisers
Anxiolytics
Better treatment for positive symptoms Hypnotics
needed:
• Widespread use of combination therapy
(app. 60 % *)
• No safety data for D2 combinations Cognitive
• No controlled studies with combinations in
schizophrenia Unserved market
segments
18
* Faries D, Ascher-Svanum H, Zhu B, Correll C, Kane J. BMC Psychiatry. 2005GlyT-1 in negative symptoms of schizophrenia
Significant reduction in negative symptom factor score*
Baseline Week 1 Week 2 Week 4 Week 6 Week 8
0
Δ PANSS negative symptom factor
–1
–2
10 mg vs placebo
–3
30 mg vs placebo
score
–4 10 mg vs placebo pConsistent effects on all measured outcomes*
Response rate CGI-I of negative symptoms
p=0.0126 Very much improved
p=0.0882 50 p=0.0255 Much improved
70 65%
60% 45 Minimally improved
No change
60 40
35 p=0.061
50
% responders
Patients (%)
43% 43%
30
40
25
30 20
20 15
10
10 5
0 Placebo RG1678 RG1678 RG1678 0 Placebo RG1678 RG1678 RG1678
10mg/day 30mg/day 60mg/day 10mg/day 30mg/day 60mg/day
Change in function (PSP)
Change from baseline Baseline
60 pGlyT-1 in phase III: exploring two indications
Negative symptoms and sub-optimally controlled patients
Negative symptoms of schizophrenia Patients with sub-optimally controlled
(3 trials) symptoms of schizophrenia (3 trials)
2x 1x 2x 1x
No. of N=620 N=620 N=600 N=600
patients 1:1:1 randomisation 1:1:1 randomisation 1:1:1 randomisation 1:1:1 randomisation
Primary PANSS negative symptoms factor score PANSS positive symptoms factor score
endpoint at week 24 at week 12
Design ARM A: 10 mg GlyT-1 ARM A: 5 mg GlyT-1 ARM A: 10 mg GlyT-1 ARM A: 5 mg GlyT-1
ARM B: 20 mg GlyT-1 ARM B: 10 mg GlyT-1 ARM B: 20 mg GlyT-1 ARM B: 10 mg GlyT-1
ARM C: placebo ARM C: placebo ARM C: placebo ARM C: placebo
Status FPI Q4 2010; Expect data 2013 FPI Q4 2010; Expect data 2013
Two new indications, study designs and patient populations agreed
with health authorities in US (SPA), Europe and Japan
21GlyT-1 development: optimizing the data quality
Synergies in study design and patient recruitment
6 months treatment 6 months treatment
Negative symptoms Extension within protocol x 3 studies
Companion studies
3 months 9 months carried out at the
same clinical sites
Partial responder Extension within protocol x 3 studies
Primary end-point read-out
Studies for negative symptoms and partial responders developed in parallel at the same clinical sites:
•High unmet medical need in both indications
•Creates broad safety data base
•Synergy in recruitment: reduced risk of rater inflation/deflation
22Treatment goal in schizophrenia
Restoring patient autonomy
Functional
and social
autonomy
Functional,
quality of life,
cognitive gains
Maintaining Stability
23
* Weiden et al, J Clin Psych 1996; 57: 53-60Ocrelizumab Humanized anti-CD20 antibody
Three major types of Multiple Sclerosis
Relapse-Remitting (RRMS) Marketplace
Mainly inflammatory
(60-65%)
Clearly defined relapses (attacks) • High unmet need:
with remissions initially returning
to baseline but gradually result in • high efficacy therapies for
sustained disability relapsing forms have major safety
issues
Inflammatory / Degenerative Secondary Progressive • no treatment for primary
(SPMS) (20-25%) progressive disease
Disability
Initial RRMS followed by disability
accumulation. Still experience • diagnosis and classification is
relapses which eventually stop difficult, often retrospective and
Relapse No Relapse can take 2-5 years
• Treatment decisions concentrated
Mainly degenerative Primary Progressive mainly in MS centers/hospitals
(PPMS) (10-15%)
Slow but nearly continuous • Payers pressure has been limited;
worsening of disease from outset
(no relapses) patients’ advocacy groups powerful in
access
Time
25
Adapted from Lublin 1996, Arnold 2004Current treatment dominated by ABCR cycling
“Between a rock and a hard place”
Available treatment options Cycle / Switch
Avonex Betaferon
interferon ß1a interferon ß1b Tysabri
natalizumab
Copaxone Rebif
glatiramer acetate interferon ß1a
A B
Efficacy
Gilenya Tysabri
fingolimod natalizumab
R C
Treatment choice:
• Efficacy/safety trade-off
• Potential risks: Initial management Failure-switch
- ABCR: Injection site reactions Switches due to flu, injection based on ABCR efficacy
- Tysabri: opport. infect.: PML, liver toxicity site reactions or injection or tolerability issues
- Gilenya: cardiovascular- , respiratory effects, frequency
livertoxicity, macular edema, lymphomas, fetal risk
26Ocrelizumab in phase II
Efficacy amongst the highest seen in RRMS
Mean no. T1 Gd-enhancing lesions Annualized Relapse Rate (ARR)
Secondary end point
4.5 1
Placebo (n=54) p=0.0014
4.0 Ocrelizumab 600 mg (n=51)
Ocrelizumab 2000 mg (n=52)
0.8 p=0.0005
3.5 IFN beta-1a (n=52)
3.0 0.636 80% 73%
0.6
2.5 Primary end point
2.0
0.4 0.364
1.5
1.0
0.2 0.169
0.125
0.5
0.0 0 0-24 0-24 0-24 0-24
0 4 8 12 16 20 24 (n=54) (n=55) (n=55) (n=54)
Weeks 0-24 Placebo Ocrelizumab Ocrelizumab IFN beta-1a
Reductions of 96 % (2000mg) and 89 % (600mg); weeks 600 mg 2000 mg
pOcrelizumab in RRMS
Looking for the next step in MS therapy
Relative reduction in Annualized Relapse Rate
90
vs placebo in a range of phase 2/3 trials
80
70
60
50
%
40
30
20
10
0
ocrelizumab natalizumab cladribine rituximab fingolimod interferon
interferon interferon
interferon glatiramer
ß-1a
ß-1a sc
sc ß-1b
ß-1bsc acetate
NOTES:
• Pattern: Solid bars represent Phase III studies; pattern = Phase II
• Trial durations vary from 6 mos. to 3 yrs; studies included different patient populations, different in/exclusion criteria, different
ARR definitions and data were collected over a time span of more than 20 years 28
• Ph II trials of laquinimod, teriflunomide, and BG12 did not show significantly better efficacy on ARR than placebo and are
not included in comparison figuresOcrelizumab Phase III program in RMS and
PMMS
Patient Primary progressive
Relapsing multiple sclerosis (RMS)
population multiple sclerosis (PPMS)
Phase III Phase III Phase III
Phase/study
OPERA I OPERA II ORATORIO
# of patients N=800 N=800 N=630
Design • 96-week treatment period: • 96-week treatment period: • 120-week treatment period:
• ARM A: Ocrelizumab 2x 300 mg IV • ARM A: Ocrelizumab 2x 300 mg IV • ARM A: Ocrelizumab 2x 300 mg IV
every 24 weeks every 24 weeks every 24 weeks
• ARM B: Rebif® (interferon β-1a) • ARM B: Rebif® (interferon β-1a) • ARM B: Placebo
Primary • Annualized relapse rate at 96 weeks • Annualized relapse rate at 96 weeks • Sustained disability progression
endpoint versus Rebif versus Rebif versus placebo by Expanded
Disability Status Scale (EDSS)
Status • Expect FPI Q3 2011 • Expect FPI Q3 2011 • FPI Q1 2011
Rebif is a registered trademarks of EMD Serono, Inc. 29We Innovate Healthcare
You can also read
