Κλινική Έρευνα … στην πράξη! Χρήστος Αντωνόπουλος MD, Ph.D. Ιατρικός ∆ιευθυντής Ιατρικό Τµήµα Roche Hellas
Κλινική Έρευνα … στην πράξη!
Χρήστος Αντωνόπουλος MD, Ph.D.Ιατρικός ∆ιευθυντήςΙατρικό ΤµήµαRoche Hellas
“Clinical trials are crucial for developing new
medicines, improving existing treatments,
boost research and
contribute to economic growth”
2
John Dalli, former EU Health Commissioner
Proprietary and confidential. For internal use only.
3
Advances in science
Scientific Knowledge
Advances in Technology
Integrated Development
Drugs + Biomarkers & Diagnostics
MET IHCCancer genomics
Bi-specific antibody
Antibody-drug conjugate
Dual acting fragment antibody
Glyco-engineered antibody
Proprietary and confidential. For internal use only.
Baseline
aPDL1 Phase I Study23% Response Rate in NSCLC
Post C2 (Week 6)
Herbst et al ASCO 2013
Proprietary and confidential. For internal use only.
6
Advances in science
Scientific Knowledge
Advances in Technology
Integrated Development
Drugs + Biomarkers & Diagnostics
MET IHCCancer genomics
Bi-specific antibody
Antibody-drug conjugate
Dual acting fragment antibody
Glyco-engineered antibodyHow can society leverage this progress?
“Partnerships benefit both industry
and academia by providing
opportunities for the sectors to work
together to explore promising new
technologies and address scientific
problems that may lead to
breakthroughs in treatments for the
most challenging diseases and
conditions”.
Tufts Center for the Study of Drug Development
Government and industry roles in R&DShould complement each other in partnership
7
National Health System
Pharmaceutical Industry
Clinical trial activity in Greece Significantly less vs. similar size EU countries
8Source: *Malone, J, “Greek science: hope in crisis; Lancet 2012 **Clinical trials submitted in marketing-authorization applications
to the European Medicines Agency 2005-2011
� Even before crisis, Greece spend
little on R&D in terms of % of GDP
– 0.6% in 2007 vs. 1.8% UK or
3.7% in Finland*
� Since crisis, significant reduction of
government funding of ~50%*
� Pharmaceutical industry maintained
investment in R&D despite difficult
environment
Clinical trials submitted in MAAs to EMA**
3
x2
x
Good quality infrastructure….
� Sufficiently large patient pool
(11m population)
� ~130 public public hospitals
� 7 medical schools
� Highest number of physicians
per capita
...limited by inadequate processes
and lack of support for CTs
� Regulatory framework
� Administrative procedures
� Complexity of approval processes
� Lack of acknowledgment of clinical
trials as investment priority
Clinical trial enironment in Greece
9Source: Athanasakis et al., National School of Public Health, Archives of Hellenic Medicines, 2012
Cautious optimism, outlook improving
How to improve environment for CTs in Greece
Rapid access to
innovative
medicines
Sustainable,
balanced
Budget
Revised
Claw Back
Mechanism
Respect for
Intellectual
Property
Rights
Predictability
and
Transparency
Payment of
outstanding
Debts
Create more favorable environment for R&D investment
Roche investing in Greece
Significant investment, increased in 2014
Investment in
Clinical Trials
Bringing
Innovative
Medicines to
Greece
Collaborations
with local
partners
Management
Trainee Program
Uninsured
Patients
Support
Program
CSR initiatives
Roche investing in Greece
Continue to heavily invest in clinical trials
Clinical Trials
Growth is closely
linked with clinical
research
investments.
31 clinical trials
in 170 centres
including > 1200
patients
Bringing
Innovative
Medicines to
Greece
Novel treatments
for Cancer
combining
medicines with
diagnostics =
Personalized
Healthcare
CLEOPATRA Study Design
13* < 6 cycles allowed for unacceptable toxicity or PD; > 6 cycles allowed at investigator discretion. HER2, human epidermal growth factor receptor 2; MBC, metastatic breast cancer; PD, progressive disease.
HER2-positive MBCcentrally confirmed
(N = 808)
Placebo + trastuzumab
1:1
Docetaxel*≥ 6 cycles
n = 406
n = 402
Pertuzumab + trastuzumab
Docetaxel*≥ 6 cycles
PD
PD
Baselga J, et al. N Engl J Med 2012; 366:109–119.
• Randomization stratified by geographic region and
neo/adjuvant chemotherapy
• Study dosing q3w:
– Pertuzumab/placebo: 840 mg loading → 420 mg maintenance
– Trastuzumab: 8 mg/kg loading → 6 mg/kg maintenance
– Docetaxel: 75 mg/m2 → 100 mg/m2 escalation if tolerated
Final OS AnalysisMedian follow-up 50 months (range 0–70 months)
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ITT population. Stratified by geographic region and neo/adjuvant chemotherapy.
CI, confidence interval; Pla, placebo; Ptz, pertuzumab.
S. Swain et al. Final overall survival (OS) analysis from the CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients (pts)
with HER2-positive metastatic breast cancer (MBC). Presidential Symposium 1.ESMO 2014.Abstract number 350O_PR14
OS
(%
)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 7060
Time (months)
HR 0.68 95% CI = 0.56, 0.84
p = 0.0002
Ptz + T + D
Pla + T + D
128104226268318371
02391179230289350
n at risk
Ptz + T + D
Pla + T + D
402
406
40.8 months
56.5months
∆ 15.7 months
ESMO 2014
Proprietary and confidential. For internal use only.
Multiple SclerosisOver 2.3M people affected worldwide
• Chronic autoimmune disease; damages
the brain & spinal cord
• Demyelination, axonal (nerve fiber)
injury and scarring
• Variable clinical course: 4 main patterns
• Treatment: interferon, disease modifying
agents
• Median age 23 years; ~2:1 female
• Second leading cause of acquired
neurologic disability in young adults:
• Visual loss
• Sensory and motor symptoms
• Loss of coordination
• Bladder/bowel dysfunction
1MSIF, Atlas of MS 2013, http://www.msif.org/includes/documents/ cm_docs/2013/m/msif-atlas-of-ms-2013-report.pdf?f=1
Proprietary and confidential. For internal use only.
Geographic Atrophy (GA)Advanced form of dry Age-related Macular Degeneration
Advanced form of dry Age-related Macular Degeneration● Progressive, degenerative disease
of the central retina (macula)● Interferes with driving, reading,
watching TV, daily living
● Accounts for ~10% legal blindness● Affects 8M people WW, ~1.2M in
US
● Genetic predisposition: complement factor H● Supports role of inflammation in etiology
No Currently Approved Standard Of Care
PROGRESSION of GEOGRAPHIC ATROPHY
Proprietary and confidential. For internal use only.
Clinical investigation of the amyloid hypothesis in Alzheimer’s Disease
Brain Amyloid Beta expression
Amyloid expression may
precede Alzheimer
symptoms by 20 years
Clinical symptoms
HYPOTHESIS:
Accumulation of amyloid
in brain drives Alzheimer
pathogenesis and leads
to neuronal dysfunction
and cognitive decline