Augment Bone Graft regulatory update

BioMimetic submitted to FDA an amendment to the PMA for Augment Bone Graft, which is under review for use as an alternative to autograft in hindfoot and ankle fusion procedures. In January, the agency asked for additional information despite an advisory panel's positive vote last year on the product (see BioCentury, Jan. 9). Additional data in the amendment show that the primary endpoint in the company's Phase III trial - non-inferiority to autograft based on fusion rates as measured by CT scan at 24 weeks - is reproducible based on new blinded inter-observer assessments of the scans (95% correlation and 87% concordance). In the response letter, FDA also requested that BioMimetic analyze a new composite endpoint that includes radiological, clinical, functional and safety parameters. An analysis of the new endpoint showed that Augment Bone Graft was non-inferior to autograft in all patient populations, including the intent-to-treat population, at 24 and 52 weeks.

The company said it believes based on discussions with the FDA's Center for Devices and Radiological Health (CDRH) that no box warning should be required for Augment. BioMimetic also said no differences exist between Augment and autograft in detailed subgroup analyses specifically requested by FDA or additional subgroups identified by the company. In subgroup analyses requested and defined by FDA, including stratification by volume of graft used and in patients with the most severe defects requiring the highest volume of graft, Augment and autograft each showed a 48% CT fusion rate for the primary endpoint. The company also said that a pharmacokinetic study showed that local implantation of a large volume of Augment in foot and ankle fusions did not lead to systemic exposure of recombinant human platelet-derived growth factor BB ( rhPDGF-BB). The company has proposed a postapproval program that includes continued follow-up of patients from the pivotal trial as well as a patient registry to continue monitoring safety as requested by FDA. ...