In vivo Assessment of AMP2, a Novel Ceramic-Binding BMP-2, in Ovine Lumbar Interbody Fusion

Study Design Assessment of bone formation in an ovine interbody fusion study. Objective To compare OsteoAdapt SP which consists of AMP-2, a modified variant of recombinant human bone morphogenetic protein (rhBMP-2) bound to a tricalcium phosphate-containing carrier, to autologous iliac crest bone graft (ICBG) in a lumbar interbody fusion model. Summary of Background Data Treatment of lumbar disc degeneration often involves spinal fusion to reduce pain and motion at the affected spinal segment by insertion of a cage containing bone graft material. Three graft materials were compared in this study - ICBG and OsteoAdapt SP (low or high dose). Methods Sheep underwent lateral lumbar fusion surgery with PEEK or Titanium interbody cages packed with OsteoAdapt SP (low or high dose) or ICBG. Outcomes were evaluated at 8-, 16- and 26- weeks. Newly formed bone quality, bone mineralization, and fusion were assessed by manual palpation, qualitative and semi-quantitative histopathology, histomorphometry, computed tomography (CT) and microCT (mCT) analysis. Results OsteoAdapt SP was implanted into 43 animals and ICBG into 21 animals (L3-L4). No group showed evidence of systemic toxicity by multiple assessments. All levels were fused by manual palpation at 26-weeks. Serial CT scans showed increasing fusion scores over time. Both doses of OsteoAdapt SP resulted in robust new bone formation and progression of fusion in the interbody cage. Range of motion tests for treatment groups were lower compared to ICBG at 8- and 16-weeks. Similarly, histology at 8-weeks demonstrated more robust new bone formation for both OsteoAdapt SP groups compared to autograft. Conclusion We have demonstrated the preclinical safety and efficacy of OsteoAdapt SP in a clinically relevant large animal model; supporting faster and more robust new bone formation within the interbody cage, comparable to or better than the gold standard, ICBG, in all measures. A large animal model spinal fusion model was used to evaluate a novel BMP2 formulation The use of a modified calcium-bound BMP2 showed healing equivalent to or better than ICBG. The controlled release kinetics of the modified BMP2 assisted healing and reduced the risk of off target effects. The study shows good safety and efficacy data.