1. Catania, 9 Marzo Prospettive della Ricerca Clinica in Italia Angela Capriati, Corporate Clinical Research- Menarini Group

2. I tempi dello sviluppo clinico registrativo impongono di definire oggi le strategie che condizioneranno le prospettive a medio-lungo termine della ricerca clinica

3. Le prospettive della ricerca clinica italiana dipendono strettamente dalla qualità ed investimenti in ricerca

4. Research and Development of a new Drug
DISCOVERY PRECLINICAL CLINICAL REGULATORY MARKETING
DEVELOPMENT DEVELOPMENT SUBMISSION AUTHORIZ.
Florence, Pomezia
Pomezia, Berlin, Pisa, Lomagna
Florence, Berlin, Barcelona
Florence, Berlin, Barcelona
Kinetics & Metabolism
Toxicology
Chemical Development
Galenics
Biotechnological Development
Molecol. Biol
Drug Design
Chemistry
Pharmacology
Phase I
Phase II
Phase III

5. Menarini R&D Sites 11 employees in year 1978 736 employees in year 2003
Berlin
Milano
Florence
Pisa
Barcelona
Rome

6. Clinical Research Mission
INTERNAZIONALIZZAZIONE
INNOVATIVITA’

7. La ricerca clinica in Italia è di fatto una ricerca clinica in Europa
Internazionalizzazione
La ricerca clinica in Italia è di fatto una ricerca clinica in Europa

8. Menarini Clinical Research
Barcelona
Florence
Berlin

9. Normative EU, ICH guidelines
La ricerca clinica italiana deve mirare ad uno sviluppo clinico non solo europeo ma mondiale
Normative EU, ICH guidelines
Scientific Advice
Nazionali, EMEA, FDA
Advisory Board Accademici

10. Medical and Social Need
Innovatività
Medical and Social Need
Risk benefit ratio
SELEZIONE
Prodotti
Aree
terapeutiche

11. INNOVATIVITA’  Nuovi prodotti e nuove strategie terapeutiche
 Nuove indicazioni
 Nuove popolazioni target

12. strategie terapeutiche
1. Nuovi prodotti e nuove
strategie terapeutiche

13. Status: Clinical Phase III
MEN 2234 Project
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
Status: Clinical Phase III

14. MEN 2234 Survival Benefit
Phase I-II Results : Immunization induced by MEN 2234 toward ovarian
TAA favours survival in 3rd line therapy of ovarian cancer

15. Watch-full Waiting Period
Epithelial Ovarian Cancer
Medical Need +
Debulking
Surgery
Chemotherapy
Tumor Response
or Stabilisation
Progressive disease
(85%)
Manteinance
of Response
Second Line Therapy
Watch-full Waiting Period
Progressive disease

16. MEN 2234 Phase III study 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

17. 2. Nuove indicazioni

18. SABARUBICIN Preclinical Evidence
potential better risk/benefit ratio
than conventional anthracyclines O H N 2 C l .
broader antitumoral activity
favourable pharmacokinetics
lower cardiotoxicity potential

19. Sabarubicin Small Cell Lung Cancer
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

20. 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.

21. 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)]

22. Sabarubicin Orphan Medicinal Product
Designation

23. 3. Nuove popolazioni target

24. SENIORS
Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure

25. SENIORS
Age and Sex of Patients in Major Placebo- Controlled Trials of ß-Blockers in CHF
Trial
ß-blocker N
Mean age
% Males
US Carvedilol
Carvedilol
1094 58 78
MERIT-HF
Metoprolol CR/XL
3991 64 77
CIBIS-II
Bisoprolol
2647 61 80
2708
BEST
Bucindolol 60 78
COPERNICUS
Carvedilol
2289 63 79
Mean 61 79

26. Prevalence of Congestive Heart Failure by Age and Sex in NHANES
SENIORS
Prevalence of Congestive Heart Failure by Age and Sex in NHANES 1 2 3 4 5 6 7 8 9 10
20-24
25-34
35-44
45-54
55-64
65-74
>74
Men
Women
Percentage (%)
Study population
in BB trials
Source: CDC/NCHS.

27. SENIORS
Ejection Fraction (%) of Patients in Major Placebo- Controlled Trials of ß-Blockers in CHF
Trial
ß-blocker N
EF%
US Carvedilol
Carvedilol
1094
22.6
MERIT-HF
Metoprolol CR/XL
3991
28.0
CIBIS-II
Bisoprolol
2647
27.5
BEST
Bucindolol
2708
23.0
COPERNICUS
Carvedilol
2289
19.8
Mean
24.9

28. SENIORS Inclusion Criteria Age >70 years
A clinical diagnosis of chronic heart failure (HF) and either of:
a) documented LVEF < 35% within previous months or
b) hospital admission within previous 1 year for congestive HF
Written consent prior to enrolment into the study

29. SENIORS
Study Protocol

30. Baseline Characteristics - Age
SENIORS
Baseline Characteristics - Age
225
200
175
150
125
Number of patients
100 75 50 25
Age (years)
Median age = 75.2 years

31. Baseline characteristics - LVEF
SENIORS
Baseline characteristics - LVEF
600
500
400
Number of patients
300
200
100
Left ventricular ejection fraction (%)
LVEF < 35%: mean value = 28.7%
LVEF > 35%: mean value = 49.2%

32. Benefit of Nebivolol vs other beta-blockers
SENIORS
Benefit of Nebivolol vs other beta-blockers
Favours
Nebivolol
Favours
Placebo
Primary outcome
SENIORS- Overall population
- Age < 75 y & LVEF < 35%
All cause mortality
SENIORS - Overall population
- Age < 75 y & LVEF < 35%
CIBIS II
MERIT
COPERNICUS
0.40
0.50
0.60
0.70
0.80
0.90
1.00
1.10
1.20
Hazard ratio and 95% CI

33. SENIORS
Fast Track

34. > 25.000 Expected Patients in Clinical Trials in 2006
24000
20000
16000
12000
8000
4000
1992
1995
2000
2006