P15 Osteogenic Cell Binding Peptide: From Ideation and Back Again
Jerome Connor
VIce President R&D, Cerapedics
The i-FACTOR family of osteobiological products is based on the biologically active P-15 osteogenic cell binding peptide. P-15 is a synthetic replicate of a 15 amino-acid sequence naturally occurring in type I collagen. The i-FACTOR products are a composite bone graft material consisting of a synthetic version of the P15 peptide adsorbed onto calcium phosphate particles, which are incorporated into an inert carrier. The calcium phosphate particles, also known as anorganic bone mineral (ABM), provide a scaffolding and source of calcium for new bone growth. The synthetic P-15 collagen fragment is a short chain peptide that mimics a cell binding domain of Type I collagen, thus providing a more favorable environment that facilitates cell attachment on the ABM scaffold.
The P-15 sequence was discovered by Dr. Rajendra Bhatnagar in the 1990 who demonstrated the peptide’s influences on cell behaviors. Based on those results and other laboratory studies on P-15’s biological activities, the responses of osteogenic cells to P-15 peptide comprise three phases. First, strong cell attachment to P-15 occurs via cell surface determinants including the integrins. Second, intracellular signaling pathways and the expression of pro-differentiation genes are activated. Third, P-15-activated cells secrete cytokines, which may osteogenic cells and amplify their differentiation culminating in robust bone regeneration.
i-FACTOR Putty is the commercial product derived from the P-15/ABM composite. This bone graft substitute underwent an IDE, Level 1 clinical trial in a ACDF surgical indication. The clinical study was, prospective, controlled, randomize, blinded and statistically powered. The end points were fusion, NDI score, neurological success, and safety. In addition, a composite “overall success” analysis was performed. The i-FACTOR putty was demonstrated to be statistically non-inferior to the control autograft arm. Moreover, the i-FACTOR putty was shown to be statistically superior to autograft in Overall Success at both the 1- and 2-year time intervals. This outcome led to the PMA approval from the FDA for i-FACTOR Putty in the ACDF indication, which is the only FDA-approved product for this surgical procedure.
Subsequently, a new P-15 peptide-based product was engineered for use in a lumbar spinal fusion indication. The P-15L product is specifically designed with enhanced handling and moldability characteristics to complement the lumbar surgical procedures. The P-15L is currently undergoing testing in an IDE, Level 1 clinical trial.
Dr. Jerome Connor received his B.S. degree in Chemistry at Lafayette College and his M.S. and Ph.D. in Biochemistry at The University of Tennessee. Dr. Connor became a post-doctoral fellow at M.D. Anderson Cancer Center at the University of Texas and then joined the facility in the Department of Cell Biology. During his academic tenure, his research was focused on membrane physiology and cell aging.
Subsequently, Dr. Connor joined the research and development department of LifeCell Corporation and over a 24-year tenure as the Senior Director his research was focused on developing soft tissue regenerative medicine products. This research lead to the successful commercialization of AlloDerm, Cymetra, Strattice, GraftJacket, Revolve and AlloCraft.
Dr Connor is currently the Vice President of R&D at Cerapedics Inc. where he leads the technical team which developed and commercializing i-FACTOR Putty, a peptide-based drug/device that is the only PMA-approve biological product indicated for use in cervical fusion. Currently the department is developing pipeline products in the ortho-biological field.