Michael A' Grosso MD

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Michael A. Grosso MD
Amirtha Naadimuthu MD
Vice-President Head, US CRU
Director Medical Advisor Cardio-Thrombosis US
CRU
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Sanofi-Aventis Diversified Products
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Diversified Portfolio
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Clinical Trials Network Clinical Research Units-
CRU- 29 CRUs WW
SWEDEN (Denmark, Estonia, Finland,
Latvia, Lithuania, Norway)
POLAND
HUNGARY (Romania, Bulgaria, Croatia)
CZECH REPUBLIC
RUSSIA (Belarus, Ukraine)
GERMANY (Austria)
NETHERLANDS
BELGIUM
CANADA
UK (Ireland)
FRANCE (Morocco, Tunisia)
JAPAN
SWITZERLAND
SPAIN
PORTUGAL
SOUTH KOREA
USA
MEXICO (Columbia, Costa Rica, Dominican
Republic, Guatemala, Panama, Peru, Venezuela
ITALY
CHINA
SINGAPORE ( Hong-Kong, Indonesia, Malaysia,
Philippines,Taïwan, Thaïland)
TURKEY
INDIA
GREECE
USA A. Naadimuthu
BRAZIL
Europe Canada B. Crepon
CHILE
Japan H. Honkawa
SOUTH AFRICA
ARGENTINA
AUSTRALIA
Intercontinental M. Sotty
China F. Jiang
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US CRU Organization and People
US Clinical Research Unit Head A.
NAADIMUTHU Deputy W. JORDAN
SAFETY
THERAPEUTICS
OPERATIONS Regional Monitoring
CVS/THR M. GROSSO
INM/MAD/RSP O. ABDULLAH
CNS B. BOCK
ONC M. ZAKI
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US CRU Organization
Total Studies 95 trials Total Patients
20,000 pts. US, 100,000 pts. global
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Clinical Trials and tribulations !!!
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Clinical Trials and tribulations !!!

• Increase in Clinical Trial Execution Burden

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Clinical Trials and tribulations !!!

• Increase in Clinical Trial Execution Burden

• Decrease in Clinical Trial Participation

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Clinical Trials and tribulations !!!

• Decrease in Clinical Trial Participation

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Clinical Trials and tribulations !!!

• Decrease in Clinical Trial Participation

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Clinical Trials and tribulations !!!

• N Engl J Med. 1979 Dec 6301(23)1254-9.
• The clinical investigator as an endangered
  species.
• Wyngaarden JB.
• Shortage Of Clinical Trials Investigators
• Predicted - 2005
• Contract negotiation (intellectual property
  publications), use of local IRBs

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Clinical Trials and tribulations !!!

• Cooperative Research and Development Agreement
  (CRADA)
• A Cooperative Research and Development Agreement
  (CRADA) is a written agreement between a private
  company and a government agency to work together
  on a project. Created as a result of the
  Stevenson-Wydler Technology Innovation Act of
  1980, as amended by the Federal Technology
  Transfer Act of 1986, a CRADA allows the Federal
  government and non-Federal partners to optimize
  their resources, share technical expertise in a
  protected environment, share intellectual
  property emerging from the effort, and speed the
  commercialization of federally developed
  technology.
• VA has master template CRADAs where no additional
  legal review of the
• CRADA body is needed NAVREF Feb 2008
• Amgen Bristol-Myers Squibb Genentech GSK
  Merck Novartis
• OncoGenex Pfizer Roche
  Sanofi-Aventis Sucampo
• VA Central Institutional Review Board

Executed VA CRADAs
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(No Transcript)
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Study Portfolio for CV-T Diseases
SHINE SEPIA-ACS1 SEPIA ACS II
Unstable angina Acute myocardial infarction
Coronary thrombosis
ACTIVE A
AUDITOR CRESCENDO STRADIVARIUS
EQUINOX CASSIOPEA SAVE AVE5026
Atrial fibrillation
Coronary disease
ATHENA BOREALIS
VTE
Stroke
TAFi CLARINET CLARINET LT
PAOD
Ventricular tachcardia fibrillation
ACCELA TAMARIS
Atherosclerosis
ALPHEE

RAVEL-1 ACTIVE I
completed enrolling pipeline
Hypertension
Death
Peripheral arterial occlusive disease
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Idrabiotaparinux Phase III enrolling studies

• BOREALIS-AF idrabiotaparinux vs VKA treatment
  of stroke prevention in AF
• N 9600 US 250 sites 2250 pts
• CASSIOPEA - idrabiotaparinux vs VKA treatment
  of PE and
  prevention of VTE
• N 3200 US 50 sites 355 pts

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• TAMARIS therapeutic angiogenesis in patients
  with critical limb ischemia using DNA
  plasmid NVG1FGF vs placebo
• N 492 Enrollment complete 6/09
• Non-viral gene therapy
• Devoid of the viral gene therapy problems (eg,
  virus integration into tumor suppressor genes or
  proto-oncogenes)

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Dronedarone Multaq
I
O
C2H5
O
N
(CH2)2
C2H5
I
O
C4H9
Amiodarone (MW682)
O
C4H9
O
N
(CH2)3
CH3SO2NH
C4H9
C4H9
O
SR33589B/Dronedarone (MW593)

• ATHENA n 4700 40 RR arrhythmic death
  30RR all CV mortality
• Potential less side effects vs. amiodarone
• First new AF AAD approved in 20 years

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ALPHEE DRI10936

• DOUBLE BLIND PLACEBO CONTROLLED DOSE RANGING
  STUDY OF THE EFFICACY AND SAFETY OF CELIVARONE AT
  50, 100 OR 300 mg OD WITH AMIODARONE AS
  CALIBRATOR FOR THE PREVENTION OF ICD
  INTERVENTIONS OR DEATH
• N 438 pts. 100 sites global ( US 148 pts / 30
  sites )
• Phase IIB
• FPI US 17-Sep-09

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AVE5026 SEMULOPARIN

• Ultra-low-molecular weight heparin
• Potent inhibitor of Factor Xa with lower residual
  anti-IIa activity ratio anti-Xa/IIagt30 (enox
  3-5) TREK
• Half-life 16-20 h (enox 4-7h)

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AVE5026 Semuloparin SAVE Program
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XRP0673 Otamixiban

• OTIMIXABAN synthetic direct factor Xa inhibitor-
• IV short acting
  10-30 min affinity thrombin
• NSTE-ACS treated invasively as target population
• Improved benefit risk, superior efficacy
• Expected duration of treatment 1-3 days
• 1-3 days (stop after procedure)
• Patient tailored and safe dosing
• Xmg/kg bolus Ymg/kg/h continuous infusion
• No dose adjustment for renal impairment
• No need for monitoring
• No PK drug-drug interactions
• 7 Phase I, 3 Phase II studies
• n 3264 ESC Lancet
  RR 0.6 p 0.02

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SEPIA - ACS II

• Non ST Elevation ACS scheduled for early invasive
  strategy (same population as SEPIA I)
• Comparator UFH eptifibatide (same as SEPIA I)
• Superiority trial (RR30)
• Primary Criteria Efficacy
• All Death Myocardial Infarction at Day 7
• Follow up 6 months
• Recruitment 8,000 pts 26 months / 650 sites

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AVE0010 GLP-1 Agonist
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• TOTAL Phase III 3845
• GETGOAL-M add-on to Met (morning vs. evening
  dosing) EFC6014
• GETGOAL-F1 add-on to Met (1-step 2-step
  titrations)
• GETGOAL-S add-on to SU /-Met EFC6015
• GETGOAL-L add-on to basal insulin /- Met
  EFC6016
• GETGOAL-P add-on to pioglitazone /- Met
  EFC6017
• GETGOAL-X add-on to Met vs. exenatide Met
  EFC6019
• GETGOAL-Mono vs placebo EFC6018
• EFC11390 Safety GLP-1 in recent ACS patients
  n 3000

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• THANK YOU
• Michael Grosso MD
• 610-889-8968 office
• 609-792-7092 cell
• Michael.grosso_at_sanofi-aventis.com