Developing a Gene-Activated Matrix Product for Chronic Wounds: A Biotech's Perspective

Background: The normal wound healing process is mediated by specific cells and cytokines, especially growth factors. In chronic wounds, there is often a deficiency of endogenous growth factors, which impairs healing. The Clinical Problem: Administration of exogenous growth factor proteins has had limited success because of inefficient delivery, inadequate persistence, and poor patient compliance with daily treatment regimens for prolonged periods of time. The Clinical Solution: If the gene encoding a growth factor could be transfected into cells in the tissue defect, prolonged production of growth factor could improve therapeutic efficacy. Formulating the DNA vector in a biocompatible matrix (Gene Activated Matrix) can further enhance the product potential. GAM501 (an adenovector encoding platelet-derived growth factor-B gene within 2.6% collagen matrix) has progressed to a phase 2b clinical trial. Market—History, Current, and Prospects: Only recombinant human plateletderived growth factor-B homodimer (becaplermin) has been approved by the U.S. Food and Drug Administration for the treatment of diabetic ulcers. There remains a compelling medical need for a more practical and effective therapy for nonhealing ulcers, which is a large and expanding market. Business Challenges—Policies & Practices: An ideal wound healing product would promote faster healing, be more effective and easier to use, and be less expensive itself or require fewer associated medical resources than current products (i.e., faster, better, and cheaper). A combination product must generally demonstrate that both components are required for efficacy, or that the combination is superior to the individual components. Public–Private Partnership—SWOT (strength, weakness, opportunities, threat) Analysis: Developing a combination wound healing product requires collaboration with the U.S. Food and Drug Administration, and gene therapy trials must be reviewed by the Recombinant DNA Advisory Committee at National Institutes of Health. Conclusion: Collaboration with regulatory agencies during all phases of clinical development and periodic reanalysis of trial design strategies and commercial plans is essential in developing combination products for wound healing.