Summary of InFUSE ™ Bone Graft Preclinical and Pilot Clinical Studies with Interbody Spinal Fusion...
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Transcript of Summary of InFUSE ™ Bone Graft Preclinical and Pilot Clinical Studies with Interbody Spinal Fusion...
Summary of InFUSESummary of InFUSE™ ™ Bone GraftBone Graft
Preclinical and Pilot Clinical Preclinical and Pilot Clinical Studies with Interbody Spinal Studies with Interbody Spinal
Fusion DevicesFusion Devices
Scott Boden, M.D.Scott Boden, M.D.Professor of Orthopaedic SurgeryProfessor of Orthopaedic Surgery
Director, The Emory Spine Center Director, The Emory Spine Center Emory University School of MedicineEmory University School of Medicine
Summary of Interbody Fusion Pre-clinical Studies with rhBMP-2/ACS(InFUSE™ Bone Graft)
Investigator Species Number ofAnimals
Follow-up Fusion Rate*
Sandhu Sheep 6-8 @ group 6 months 37% autograft100% rhBMP-2
Zdeblick Goats 21 @ group 3 months 48% autograft95% rhBMP-2
Boden Monkeys 3 @ group 6 months 0% sponge only100% rhBMP-2
Hecht Monkeys 3 @ group 6 months 33% autograft100% rhBMP-2
*Fusion assessed via histology in animal studies
rhBMP-2/ACS vs AutograftrhBMP-2/ACS vs Autograft
Model:Model: Single level interbody fusion with titanium cage in sheep Single level interbody fusion with titanium cage in sheep modelmodel
Duration:Duration: Six months Six months
Study Groups: (n)Study Groups: (n)Cage & autograft Cage & autograft 8 8Cage & rhBMP-2/ACS Cage & rhBMP-2/ACS 66
Sandhu, Dawson et al., Spine, In Press 2002
Sandhu, Dawson et al., Spine, In Press 2002
rhBMP-2/ACS vs AutograftrhBMP-2/ACS vs Autograft
100% 100%
37%
100%
0%
20%
40%
60%
80%
100%
Autograft rhBMP-2/ACS
Fus
ion
Rat
e
Plain X-Ray
Histologic
Autograft Control
rhBMP-2/ACS
Biomechanical Test ResultsBiomechanical Test ResultsrhBMP-2/ACS = AutograftrhBMP-2/ACS = Autograft
0
10
20
30
Stif
fnes
s (N
.m/d
egre
e)
Unoperatedcontrol
Titanium cage +autograft
Titanium cage +rhBMP-2
rhBMP-2/ACS vs AutograftrhBMP-2/ACS vs Autograft
Model:Model: Single level interbody fusion with titanium cage in goat Single level interbody fusion with titanium cage in goat modelmodel
Duration:Duration: Six months Six months
Study Groups: (n)Study Groups: (n)Cage & autograft Cage & autograft 2121Cage & rhBMP-2/ACS 21Cage & rhBMP-2/ACS 21
Zdeblick et al., Spine, 1998
Zdeblick et al., Spine, 1998
rhBMP-2/ACS vs AutograftrhBMP-2/ACS vs Autograft
100%
48%
95%86%
0%
20%
40%
60%
80%
100%
Autograft rhBMP-2/ACS
Fus
ion
Ra
te Plain X-Ray
Histologic
Biomechanical Test ResultsBiomechanical Test Results
• No statistical difference in stiffness No statistical difference in stiffness between autograft and rhBMP-2 fusionsbetween autograft and rhBMP-2 fusions
• rhBMP-2/ACS = AutograftrhBMP-2/ACS = Autograft
Rabbit Posterolateral Fusion ModelRabbit Posterolateral Fusion Model
Autograft 42% fusion
rhBMP-2/ACS
100% fusion Schimandle, Boden, et. al., Spine 1995
Strength of Bone Generated with Strength of Bone Generated with rhBMP-2/ACS vs AutograftrhBMP-2/ACS vs Autograft
0
0.5
1
1.5
2
2.5
3
Relative Strength Relative Stiffness
rhBMP-2/ACS
Autograft
Rel
ativ
e to
ad
jace
nt
un
fuse
d l
evel
Schimandle, Boden, et. al., Spine 1995
rhBMP-2/ACS vs Autograft in rhBMP-2/ACS vs Autograft in Non-Human PrimatesNon-Human Primates
Model:Model: Rhesus monkey, single level Rhesus monkey, single level interbody fusion interbody fusion
Duration:Duration: Six months Six months
Study Groups: (n)Study Groups: (n)Allograft bone dowel + autograft Allograft bone dowel + autograft 3 3Allograft bone dowel + rhBMP-2/ACS Allograft bone dowel + rhBMP-2/ACS 33
Fishgrund, Herkowitz et al., Spine,1999Fishgrund, Herkowitz et al., Spine,1999
Preclinical Study Results (3 months)Preclinical Study Results (3 months)
Fishgrund, Herkowitz et al., Spine, 1999
rhBMP-2/ACSrhBMP-2/ACSControlControl
ControlControl(50%)(50%)
Preclinical Study ResultsPreclinical Study Results (6 Months) (6 Months)
rhBMP-2/ACSrhBMP-2/ACS(100%)(100%)
Fishgrund, Herkowitz et al., Spine,1999
rhBMP-2/ACS in Non-Human rhBMP-2/ACS in Non-Human PrimatesPrimates
Model:Model: Rhesus monkey, single level Rhesus monkey, single level interbody fusioninterbody fusion
Duration:Duration: Six months Six months
Study Groups:Study Groups:
(n) (n)Cage + buffer/ACS Cage + buffer/ACS 2 2 Cage + 0.75mg/mL rhBMP-2/ACS Cage + 0.75mg/mL rhBMP-2/ACS 2 2 Cage + 1.50mg/mL rhBMP-2/ACSCage + 1.50mg/mL rhBMP-2/ACS 3 3
Boden, Sandhu et al., J. Spine Disorders, 1998Boden, Sandhu et al., J. Spine Disorders, 1998
6 Month Fusion Results (%)6 Month Fusion Results (%)
ControlControl (0%)(0%)
0.75 mg/mL rhBMP-2/ACS0.75 mg/mL rhBMP-2/ACS (100%)(100%)
1.50 mg/mL rhBMP-2/ACS1.50 mg/mL rhBMP-2/ACS(100%)(100%)
Boden, Sandhu et al., J. Spine Disorders, 1998
Collagen Sponge
only(6
months)
Collagen Sponge
+rhBMP-2
(6 months)
Boden, Sandhu, et al., J. Spinal Disorders 1998
Collagen Sponge
+rhBMP-2
(6 months)
Boden, Sandhu, et al., J. Spinal Disorders 1998
InFUSE™ Bone Graft/LT-CAGE™ InFUSE™ Bone Graft/LT-CAGE™ Pilot Clinical Study DesignPilot Clinical Study Design
4 Investigators4 Investigators
Study Groups:Study Groups: (n)(n)
LT-CAGE & InFUSE™ Bone Graft LT-CAGE & InFUSE™ Bone Graft 1111
LT-CAGE & AutograftLT-CAGE & Autograft 33
Boden, Zdeblick, Sandhu, and Heim, Spine, 2000
InFUSE™ Bone Graft/ InFUSE™ Bone Graft/ LT-CAGE™ Device LT-CAGE™ Device
Human Pilot Study ResultsHuman Pilot Study Results
Fusion rateFusion rate
InFUSE™InFUSE™ Bone GraftBone Graft 11/11 11/11 (100%)(100%)
Autograft 2/3 (66%)Autograft 2/3 (66%)
Boden, Zdeblick, Sandhu, and Heim, Spine, 2000
InFUSE™ Bone Graft/LT-CAGE™ InFUSE™ Bone Graft/LT-CAGE™ Device Pilot Study - Oswestry ResultsDevice Pilot Study - Oswestry Results
05
1015
202530
3540
4550
Os
we
str
y M
ea
n
InFUSE
Autograft
Boden, Zdeblick, Sandhu, and Heim, Spine, 2000
Serial CT Review-Autograft PatientSerial CT Review-Autograft Patient
RightRightCageCage
Left Left CageCage
Coronal Coronal ViewView
Serial CT Review-Autograft PatientSerial CT Review-Autograft Patient
RightRightCageCage
Left Left CageCage
Coronal Coronal ViewView
Serial CT Review-InFUSESerial CT Review-InFUSE™™ Bone Graft PatientBone Graft Patient
RightRightCageCage
Left Left CageCage
Coronal Coronal ViewView
Serial CT Review-InFUSESerial CT Review-InFUSE™ ™
BoneBone Graft PatientGraft Patient
RightRightCageCage
Left Left CageCage
Coronal Coronal ViewView
Goals of rhBMP-2/ACS DeviceGoals of rhBMP-2/ACS Device• Safety - no bone formation away from Safety - no bone formation away from
the cagesthe cages
• Effectiveness Effectiveness
–eliminate bone grafting morbidityeliminate bone grafting morbidity
–equal or better healing successequal or better healing success
• Goal of rhBMP-2/ACS is to make bone!Goal of rhBMP-2/ACS is to make bone!
Conclusions -Conclusions - • rhBMP-2/ACS has success >95% in 4 preclinical rhBMP-2/ACS has success >95% in 4 preclinical
studies, substantially better than control (<50%)studies, substantially better than control (<50%)• Bone formed is normal and biomechanically Bone formed is normal and biomechanically
equal to autograftequal to autograft• CT scan analysis correlates well with histology CT scan analysis correlates well with histology
of rhBMP-2 bone formationof rhBMP-2 bone formation• The concentration of rhBMP-2 successful in The concentration of rhBMP-2 successful in
rhesus monkeys produced same 100% success rhesus monkeys produced same 100% success in human pilot clinical trialin human pilot clinical trial