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