Critical Path Institute Announces New Board Members Bonnie A. Allin and Louis Breton
Critical Path Institute (C-Path) today announced the appointments of Bonnie A. Allin and Louis Breton to its Board of Directors.
Chronic kidney disease (CKD) is one of the leading causes of death in the United States, affecting about 37 million people. Of those affected, approximately 786,000 have end-stage kidney disease, and about 228,000 are living with a kidney transplant. By far, the largest unmet need in kidney transplantation is improvement in the long-term survival of the transplant recipient and graft. Current Immunosuppressive Therapy (IST) regimens have dramatically improved short-term outcomes, with one-year graft survival rates of 97.3% and 93.3% for living and deceased donor transplants, respectively.
Despite these improved short-term outcomes, long-term graft survival remains suboptimal. The 5 and 10-year graft survival rates are 77% and 49% for deceased donor transplants and 86% and 64% for living donor transplants. Consequently, there is a significant need for ISTs that are superior to current therapies and can help improve long-term outcomes.
National Data—OPTN. (n.d.). Retrieved December 12, 2019. View source
In 2017, the American Society of Transplantation (AST) and American Society of Transplant Surgeons (ASTS) partnered with Critical Path Institute (C-Path) and other transplant community members to create the TTC. By facilitating a public-private partnership among scientists from the bio-pharmaceutical industry, diagnostics companies, academic institutions, professional societies, and government and regulatory agencies, TTC fosters consensus and data-driven research to speed the development of new ISTs for transplant recipients.
TTC’s focus has primarily been on gaining regulatory endorsement of an early novel endpoint that is capable of predicting long-term graft survival in pivotal clinical trials designed to support regulatory approval of new ISTs for kidney transplantation.
To develop a novel trial endpoint, it is important to understand the multifactorial causes of late kidney graft failure; predicting failure accurately with a single marker may not be optimal. In 2019, the Paris Transplant Group (PTG), together with 29 key opinion leaders of the transplant community from ten referral centers in Europe and the United States, published a paper on the iBOX risk prediction tool.
iBOX utilizes multiple clinically relevant features that are mechanistically associated with an increased risk of late graft functional decline and failure. iBOX was originally designed to be used at the patient level to inform clinical care and management of kidney transplant patients. While several composite scores have been proposed as surrogates, iBOX is based on the largest dataset and the only specifically designed multivariate model that predicts long-term graft failure.
C-Path, in collaboration with the PTG, is seeking to translate the work from the 2019 Loupy, et al., publication into a regulatory endpoint in hopes of stimulating the introduction of innovative ISTs into transplantation and streamlining drug development by facilitating clinical trials of shorter duration (i.e., one year) that can predict allograft survival.
In 2020, TTC received a Letter of Intent Determination from FDA accepting iBOX into the Biomarker Qualification Program.
In 2022, TTC developed an integrated international kidney transplant database comprised of about 23,000 kidney transplant recipients from 31 total cohorts and clinical trials to support TTC initiatives. Of these, 13,000 kidney transplant recipients from 16 transplant centers and five clinical trials are standardized to the Clinical Data Interchange Standards Consortium (CDISC).
The long-term goal of the TTC is to accelerate the medical product development process for transplantation, identifying 1) areas that have hindered product development, 2) potential biomarkers, endpoints, quantitative tools, or process improvements as solutions to address those areas, and 3) appropriate pathways to achieve regulatory endorsement for developed solutions. The consortium is first focusing on kidney transplant and long-term graft survival but may expand to other solid organ transplants in the future.
The Critical Path Institute’s experience and track record of success is leveraged to provide a framework to obtain the regulatory agency endorsement of new tools, ensuring regulatory acceptability when implemented in individual product development programs.
C-Path has extensive experience in the aggregation of data from various sources across therapeutic areas. Data sharing with C-Path occurs in a secure manner in keeping with all international regulations. The C-Path Data Collaboration Center (DCC) was founded to provide large-scale data solutions for C-Path’s consortia’s scientific research, with the ability to develop customized data platforms for improved collaboration.
Seeking regulatory endorsement of the Composite Biomarker Panel used in the first year after transplantation is a reasonably likely surrogate endpoint for the five-year risk of allograft loss in kidney transplant patients for use as a co-primary endpoint in conjunction with efficacy failure in clinical trials to support evaluation of immunosuppressive therapy applications submitted via the Accelerated Approval Program.
Amanda Klein, PharmD, CDCES
Executive Director, Transplant Therapeutics Consortium
Nicole Spear, MS
Senior Project Manager
Hailey Davenport
Project Manager
William E. Fitzsimmons, PharmD,
MS, Senior Advisor
Luke Kosinski, PhD, Senior Quantitative Medicine Scientist
Eric Frey, Senior Data Manager