FDA Accepts New Biomarker for Transplant Research Thanks to Tucson’s Critical Path Institute

Critical Path Institute (C-Path) announced today that its Transplant Therapeutics Consortium (TTC) has received a positive response to its Letter of Intent (LOI) from the U.S. Food and Drug Administration (FDA) detailing the decision to accept the Composite Biomarker Panel (iBox Scoring System) into the Center for Drug Evaluation and Research (CDER) Biomarker Qualification Program (BQP).

In its LOI, TTC provided information to support the qualification of the iBox Scoring System for its proposed context of use (COU) as a reasonably likely surrogate endpoint in clinical trials intended to evaluate immunosuppressive therapies (ISTs) for individuals living with a kidney transplant. Qualification as a surrogate or reasonably likely surrogate endpoint would allow drug sponsors to pursue accelerated approval, removing a significant barrier to kidney transplant drug development.

FDA indicated in its LOI Decision Letter that it supports the consortium’s intent to pursue biomarker qualification and invited TTC to submit a Qualification Plan, the stage two submission that details how the consortium’s will demonstrate the clinical and analytical validity of the Composite Biomarker Panel, for its intended COU. In its Decision Letter, FDA stated, “Based on our review of the LOI, we agree there is an unmet need, and the development of this composite scoring system to predict patient’s long-term outcomes in clinical trials will facilitate the development of novel immunosuppressive therapies.”

Long-term graft failure rates after kidney transplantation remain unacceptably high, despite improved short-term outcomes, with 10-year all-cause graft failure approaching 50% (Hart et al., 2019). Survival of the transplanted organ has been rated, by patients, as the most important outcome, including the overall survival of the patient (Howell et al., 2012). The iBox Scoring System, developed by the Paris Transplant Group, is the first tool of its kind to seek regulatory qualification for use in kidney transplant clinical trials. To date, no biomarkers have been qualified for use as a surrogate or reasonably likely surrogate endpoint in any therapeutic area.

“This project is a meaningful example of what can be achieved by public-private-partnerships at the interface of translation science,” said TTC Executive Director Inish O’Doherty, Ph.D. Through collaboration and data sharing in the pre-competitive space, we are elevating the entire field of drug development in transplantation and working to improve the lives of those living with a kidney transplant.”

The iBox Scoring System is a risk prediction tool that combines measurements of kidney function, immunological status, and pathological assessment of kidney biopsy histology to predict the risk of graft-loss up to seven years after the time of risk assessment. The iBox Scoring System has been extensively validated for use in the treatment of individual patients in the clinical care setting. TTC, in close collaboration with the Paris Transplant Group, is seeking to translate this work into the regulatory setting for use in drug development programs. If qualified as a reasonably likely surrogate endpoint, the Composite Biomarker Panel (iBox Scoring System) will be publicly available and facilitate any drug sponsor seeking accelerated approval of novel agents, significantly reducing the time required to bring a new therapeutic agent to patients.

The iBox Scoring System will allow for greater application in drug development and lead to better therapies for patients,” said Alexandre Loupy, M.D., Ph.D., head of the National Institute of Medical Research (Inserm) U970. Loupy is a professor of Nephrology at Necker Hospital in Paris and a founder of the Paris Transplant Group. He has led the development of the iBox Scoring System over the past 10 years.

As part of the 21st Century Cures Act, passed into law in December 2016, public-private partnerships consisting of government entities, including FDA, the biopharmaceutical industry, healthcare providers, academic researchers, and patient advocacy organizations are encouraged to work together to foster innovation in drug development through drug development tools that facilitate patient access to life-saving medications.

“Long-term transplant outcomes are still suboptimal, and people living with a kidney transplantation need novel anti-rejection medications with better long-term graft survival,” said Mark Stegall, M.D., Clinician Investigator, Department of Surgery, Mayo Clinic. “Improving long-term kidney graft survival would mean patients are less likely to need a second transplant during their lifetime and would allow them to lead longer and healthier lives. The positive response letter from FDA takes us one step closer to having new therapies that better the lives of transplant recipients.”

Ken Newell, M.D., Ph.D., past-president of AST and co-chair for TTC’s Endpoints and Efficacy Working Group said, “TTC has been instrumental in bringing together partners from industry, academia, and professional societies for this groundbreaking endeavor. This effort is a labor of love, and I’m honored to be part of this consortium and to be working with colleagues across the globe with a shared mission.”

About the Organizations:

Critical Path Institute (C-Path) is an independent, nonprofit organization established in 2005 as a public and private partnership. C-Path’s mission is to catalyze the development of new approaches that advance medical innovation and regulatory science, accelerating the path to a healthier world. An international leader in forming collaborations, C-Path has established numerous global consortia that currently include more than 1,600 scientists from government and regulatory agencies, academia, patient organizations, disease foundations, and dozens of pharmaceutical and biotech companies. C-Path US is headquartered in Tucson, Arizona and C-Path, Ltd. EU is headquartered in Dublin, Ireland, with additional staff in multiple other locations. For more information, visit www.c-path.org and  c-path.eu.

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