Bezeotermin Alfa (rhBMP-6) Administration in Lumbar Interbody Fusion Surgery Using a Posterior Approach

Background: Novel osteoconductive and osteoinductive therapies for posterior-based lumbar interbody fusion surgery are needed. Bezeotermin alfa (recombinant human bone morphogenetic protein [rhBMP]-6, previously referred to as AGA111) is a potential potent stimulator of bone regeneration. This prospective, multicenter, randomized, double-blinded, placebo-controlled Phase-2 trial evaluated the safety and preliminary efficacy of bezeotermin carried by autologous blood coagulum (ABC) in patients undergoing lumbar interbody fusion surgery between L3 and S1 for degenerative disc disease. Methods: Adult patients scheduled for single-level elective lumbar interbody fusion surgery across 6 clinical trial sites in the People’s Republic of China were randomized 1:1:1 to placebo, 0.25 mg bezeotermin, or 0.5 mg bezeotermin and followed for 12 months. The primary end point was the incidence of adverse events (AEs). Secondary end points included anti-rhBMP-6 antibodies, the success rate of radiographic fusion, changes in the Oswestry Disability Index (ODI) score, changes in the pain score on a visual analogue scale (VAS), and serum drug concentrations. Results: Sixty-three patients with a mean age of 59.2 years (52% female, 98.4% Han) were enrolled in the study. Twenty-one, 20, and 22 of the patients were randomized to placebo, 0.25 mg bezeotermin, and 0.5 mg bezeotermin, respectively. All patients reported at least 1 AE during the study, but most AEs were mild to moderate in severity. No drug-related serious AEs were reported in the bezeotermin groups. There was a trend toward a higher rate of successful radiographic fusion and greater improvement of the ODI and VAS scores in the bezeotermin groups than in the placebo group from month 3 to month 12. Conclusions: This prospective, randomized, double-blinded, placebo-controlled trial demonstrated that bezeotermin/ABC was safe and well tolerated during posterior-based single-level lumbar interbody fusion. The preliminary efficacy of bezeotermin in accelerating spinal fusion and improving clinical outcomes supports its further clinical development. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.