Mr DE GARIDEL - Ingenierie Moleculaire - Forum Santé 11

GIPSO
3 EME FORUM NATIONAL DE
SANTE BORDEAUX
11 DECEMBRE 2008
Ingénierie
Moléculaire
Marc de Garidel
VP Amgen international
Region Sud

L‘ innovation en biotechnologie
avance vite et prend différentes
formes
1) Modification d’une protéine existante
2) Assemblage de molécules
3) Développement de nouvelles molécules

1)
1)1)
1)
1)
1)1)
1)
Modification
Modification Modification
Modification
Modification
Modification Modification
Modification
d’une
d’uned’une
d’une
d’une
d’uned’une
d’une
protéine
protéineprotéine
protéine
protéine
protéineprotéine
protéine
existante
existanteexistante
existante
existante
existanteexistante
existante
Darbepoetin
Darbepoetin
α
α
lpha
lpha Molecular Structure Molecular Structure
Darbepoetin
DarbepoetinDarbepoetin
Darbepoetin
Darbepoetin
DarbepoetinDarbepoetin
Darbepoetin alfa
alfaalfa
alfa
alfa
alfaalfa
alfa has:
has:has:
has:
has:
has:has:
has:
Two additional Two additional sialic sialic acid acid– –containing carbohydrates (red) containing carbohydrates (red)
Up to 8 additional Up to 8 additional sialic sialic acids acids
Increased molecular weight (~37,100 Increased molecular weight (~37,100 daltons daltons) )
Darbepoetin
DarbepoetinDarbepoetin
Darbepoetin
Darbepoetin
DarbepoetinDarbepoetin
Darbepoetin
rHuEPO
rHuEPOrHuEPO
rHuEPO
rHuEPO
rHuEPOrHuEPO
rHuEPO

Darbepoetin
Darbepoetin α αlfa lfa
Unique molecular structure Unique molecular structure
1
1
Longer half Longer half- -life life
2
2– –4 4
Greater Greater
in vivo
in vivo
biological activity
biological activity
2,5,6
2,5,6
Potential for extended and more convenient Potential for extended and more convenient
dosing schedules
dosing schedules
2,5,7
2,5,7
associated with possible
associated with possible
dose savings ( nephrology)
dose savings ( nephrology)
1. Egrie J et al. Br J Cancer 2001;84(suppl 1):3–10
2. Glaspy J et al. Br J Cancer 2002;87:268–76
3. Heatherington A et al. Br J Cancer 2001;84(suppl 1):11–6
4. Macdougall I et al. J Am Soc Nephrol 1999;10:2392–5
5. Heatherington A et al. Proc ASCO 2001;20:119A
6. Smith R et al. Br J Cancer 2001;84(suppl 1):24–30
7. Vansteenkiste J et al. J Natl Cancer Inst 2002;94:1211–20

Darbepoetin
Darbepoetin α αlfa lfa QW significantly reduced QW significantly reduced
RBC transfusion requirements
RBC transfusion requirements
Patients
Patients transfused
transfused (%)
(%)
27
27 28
28
p
p<0.001 <0.001
n=148
n=148
57
57
n=158
n=158
n=156
n=156
Week 5
Week 5– –EOTP EOTP Week 1 Week 1– –EOTP EOTP
n=149
n=149
52
52
p
p<0.001 <0.001
70
70
60
60
50
50
40
40
30
30
20
20
10
10
0
0
Vansteenkiste
Vansteenkiste J et al. J et al. J J Natl Natl Cancer Inst Cancer Inst 2002;94:1211 2002;94:1211– –20 20
Darbepoetin
Darbepoetin alfa alfa
(2.25
(2.25 µ µg/ g/kg QW) kg QW)
Placebo
Placebo