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Catania, 9 Marzo 2005
Prospettive della Ricerca Prospettive della Ricerca Clinica in ItaliaClinica in Italia
Angela Capriati, Corporate Clinical Research- Menarini Group
I tempi dello sviluppo clinico
registrativo impongono di
definire oggi le strategie che
condizioneranno le prospettive
a medio-lungo termine della
ricerca clinica
Le prospettive della ricerca
clinica italiana dipendono
strettamente dalla qualità ed
investimenti in ricerca
Research and Development of a new Drug
DISCOVERY PRECLINICAL CLINICAL REGULATORY MARKETING
DEVELOPMENT DEVELOPMENT SUBMISSION AUTHORIZ.
Florence, PomeziaPomezia, Berlin, Pisa, Lomagna
Florence, Berlin, Barcelona
Florence, Berlin, Barcelona
Molecol. Biol
Drug Design
Chemistry
Pharmacology
Kinetics & Metabolism
Toxicology
Chemical Development
Galenics
Biotechnological Development
Phase I
Phase II
Phase III
BerlinBerlin
BarcelonaBarcelona RomeRome
FlorenceFlorencePisaPisa
Menarini R&D Sites 11 employees in year 1978 736 employees in year 2003
MilanoMilano
Clinical Research Mission
INNOVATIVITA’
INTERNAZIONALIZZAZIONE
Internazionalizzazione
La ricerca clinica in Italia è di fatto una ricerca clinica in Europa
Barcelona
Florence
Berlin
Menarini Clinical Research
Nazionali, EMEA, FDA
La ricerca clinica italiana deve mirare ad uno sviluppo clinico non solo europeo ma mondiale
Scientific Advice
Advisory Board Accademici
Normative EU, ICH guidelines
Medical and Social Need Risk benefit ratio
SELEZIONE
Aree terapeutiche
Prodotti
Innovatività
INNOVATIVITA’
Nuovi prodotti e nuove strategie terapeutiche
Nuove indicazioni
Nuove popolazioni target
1. Nuovi prodotti e nuove strategie terapeutiche
MEN 2234 Project
Status: Clinical Phase III
Therapeutic vaccine:
it acts as a murine monoclonal anti-idiotype antibody mimicking the structure of CA 125, the Tumor Associated Antigen (TAA) over-expressed on epithelial ovarian cancer
Phase I-II Results : Immunization induced by MEN 2234 toward ovarian
TAA favours survival in 3rd line therapy of ovarian cancer
MEN 2234 Survival Benefit
Debulking Surgery
Chemotherapy
Progressive disease
Second Line Therapy
Tumor Response or Stabilisation
Watch-full Waiting Period
Progressive disease
+
Manteinance of Response
Epithelial Ovarian Cancer Medical Need
(85%)
Total number of patients to be randomised: 1164 (n=582 per arm)
2 year recruitment + 2 year min follow up
>150 Investigational Sites to be activated in EU and USA
MEN 2234 Phase III study
2. Nuove indicazioni
potential better risk/benefit ratio
than conventional anthracyclines
O
O
O H
O H
O H O
O
O
O
O H
O H
O
H ON H2 H C l.
SABARUBICIN Preclinical Evidence
• broader antitumoral activity
• favourable pharmacokinetics
• lower cardiotoxicity potential
• rare disease (year prevalence < 5 cases / 10,000)
• first line chemotherapy used always as combination regimens (EP, CAV, CEV)1 with limited impact on survival but significant toxicity
• very poor prognosis (median survival <12 months despite of its high chemosensitivity)
High medical need for new chemotherapy with improved efficacy and/or improved safety
1 EP= etoposide-cisplatin; CAV/CEV=Cyclophosphamide+adriamicine/epirubicine+vincristine
Sabarubicin Small Cell Lung Cancer
Sabarubicin Phase II Clinical evidence
• Most promising antitumoral activity (response rate, survival) as single agent in phase II clinical trial recruiting patients with SCLC-ED;
• Incidence and severity of toxicity (including class-related myelotoxicity and cardiotoxicity) in the overall six phase II studies lower than expected for anthracyclines.
Sabarubicin Orphan Medicinal Product Designation
According to Regulation (EC) No 141/2000 of the European Parliament and of the Council of the European Union the designation of orphan medicinal product for the indication of SCLC was sought
• as treatment of a disease affecting not more than 5 in 10,000 persons in the Community [Art. 3 (1) (a)]
and
• as a medicinal product which will be of significant benefit to those affected by that condition [Art. 3 (1) (b)]
Sabarubicin Orphan Medicinal Product Designation
3. Nuove popolazioni target
Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors
with Heart Failure
SENIORSSENIORS
612647BisoprololCIBIS-II
643991Metoprolol CR/XLMERIT-HF
581094CarvedilolUS Carvedilol
61Mean
632289CarvedilolCOPERNICUS
602708BucindololBEST
Mean ageNß-blockerTrial
Age and Sex of Patients in Major Placebo-Controlled Trials of ß-Blockers in CHF
% Males
77
78
80
78
79
79
SENIORS
Prevalence of Congestive Heart Failure by Age and Sex in NHANES
Source: CDC/NCHS.
00
11
22
33
44
55
66
77
88
99
1010
20-2420-24 25-3425-34 35-4435-44 45-5445-54 55-6455-64 65-7465-74 >74>74
MenMen WomenWomen
Per
cen
tag
e (%
)P
erce
nta
ge
(%)
Study populationin BB trials
SENIORS
27.52647BisoprololCIBIS-II
28.03991Metoprolol CR/XLMERIT-HF
22.61094CarvedilolUS Carvedilol
24.9Mean
19.82289CarvedilolCOPERNICUS
23.02708BucindololBEST
EF%Nß-blockerTrial
Ejection Fraction (%) of Patients in Major Placebo-Controlled Trials of ß-Blockers in CHF
SENIORS
• Age >70 years• A clinical diagnosis of chronic heart failure (HF) and either
of:
a) documented LVEF < 35% within previous 6 months
or
b) hospital admission within previous 1 year for congestive HF
• Written consent prior to enrolment into the study
SENIORS Inclusion Criteria
Study ProtocolSENIORS
0
25
50
75
100
125
150
175
200
225
Age (years)
Nu
mb
er o
f p
atie
nts
70 75 80 85 90 95
Median age = 75.2 years
SENIORS Baseline Characteristics - Age
0
100
200
300
400
500
600
10 -
1415
- 19
20 -
2425
- 29
30 -
3435
- 39
40 -
4445
- 49
50 -
5455
- 59
60 -
6465
- 69
70 -
7475
- 80
Left ventricular ejection fraction (%)
Nu
mb
er o
f p
atie
nts
LVEF < 35%: mean value = 28.7% LVEF > 35%: mean value = 49.2%
Baseline characteristics - LVEFSENIORSSENIORS
0.40 0.50 0.60 0.70 0.80 0.90 1.00 1.10 1.20
Hazard ratio and 95% CI
Benefit of Nebivolol vs other beta-blockersFavours Nebivolol
Favours Placebo
Primary outcomeSENIORS- Overall population
- Age < 75 y & LVEF < 35%
All cause mortalitySENIORS - Overall population
- Age < 75 y & LVEF < 35%
CIBIS II
MERIT
COPERNICUS
SENIORS
Fast TrackSENIORS
> 25.000 Expected Patients in Clinical Trials in 2006
0
4000
8000
12000
16000
20000
24000
1992 1995 2000 2006