Strategies to Improve Novel Drug Development in Kidney Transplantation Through the Clinical Trials Process.

Kidney transplantation has emerged as the preferred treatment for end-stage renal disease. Despite excellent short-term outcomes with standard T-cell centric immunosuppression, long-term outcomes have not improved. Indeed, approximately 5,000 renal allografts fail in the United States each year. Until recently, the focus on causes for late graft failures was on calcineurin inhibitor toxicity and the effects of primary co-morbid conditions (i.e., diabetes and hypertension) or recurrent glomerular diseases. However, several recent studies have identified donor-specific antibodies and chronic antibody-mediated rejection as the primary causes of late allograft failures. This finding has resulted in a renaissance of interest in the development of new agents focused on modifying B cells and alloantibody responses. In 2015, the Food and Drug Administration (FDA) held a conference of experts focused on delineating a path forward for developing a more streamlined clinical trials process to obtain labeling for novel agents in transplantation. The particular focus was on developing new drugs to deal with desensitization and prevention and treatment of antibody-mediated rejection since there are currently no approved drugs in this area. In this manuscript, we will discuss each of these important issues in depth, with particular focus on how to improve the clinical trials process to obtain FDA approval for new drugs that would be of benefit to our patients. It is also encouraging that since the FDA meeting, two new labeling trials have gone forward and one has already begun patient entry.