Transplant Therapeutics Consortium Receives FDA Acceptance of the Qualification Plan for iBox Scoring System

The iBox Scoring System is a novel endpoint predictive of long-term survival after kidney transplantation

MOUNT LAUREL, N.J., Nov. 20, 2024 /PRNewswire/ -- The American Society of Transplant Surgeons (ASTS) and American Society of Transplantation (AST) announced today that the Transplant Therapeutics Consortium (TTC) received notification from FDA of acceptance of the Qualification Plan for the iBox Scoring System, a novel reasonably likely surrogate efficacy endpoint for kidney transplant clinical trials. This takes us one step closer to having new therapies that better the lives of transplant recipients and marks the successful completion of step two in the three-step process for FDA biomarker qualification. The iBox scoring system is the first transplant endpoint to reach this stage of qualification.

"With the iBox Scoring System on the pathway to FDA qualification, we are closer than ever to cutting-edge clinical tools that could extend the lives of transplant recipients. iBox is opening the door to using artificial intelligence and machine learning. This achievement signals a transformative shift in how we approach clinical trials for transplant patients and is a critical step forward in modernizing the field," said AST President Jon Kobashigawa, MD.

Improving the long-term survival of transplanted kidneys is an important area of unmet need for transplantation recipients, and clinical trials testing new immunosuppressive agents are needed to improve kidney transplant outcomes. Although the current efficacy failure endpoint has typically shown the non-inferiority of immunosuppressive regimens, the iBox Scoring System is proposed to be used to demonstrate the superiority of a new agents compared to the standard of care (SOC) as a co-primary endpoint in pivotal drug therapeutic studies. As a reasonably likely surrogate endpoint, the iBox scoring system would be used in the Accelerated Approval Pathway at the FDA designed to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need.

"We are delighted that the iBox which received endorsement and qualification by the European Medicines Agency (EMA) in 2022 now also has received acceptance of the FDA Biomarker Qualification Plan as an efficacy endpoint for kidney transplant clinical trials. This acceptance will facilitate more rapid assessment of novel Immunotherapeutics for kidney transplant recipients and harmonization of multinational clinical trials. We are grateful to our many partners and collaborators in the Transplant Therapeutics Consortium for their steadfast support of this important initiative to facilitate innovation in transplantation," said ASTS President Ginny Bumgardner.

"We desperately need new regulatory pathways which bring investment into transplantation. New therapies are essential to prolong the life of transplant recipients and take the best care of the gift of life provided by our donors" said Dr. Karin Hehenberger, President Lyfebulb, and a kidney and pancreas transplant recipient. "This step is critical to enable the dream of 'One Kidney for Life' to become a reality."

The iBox scoring system is a composite endpoint used as a risk prediction tool that utilizes multiple clinically relevant features (estimated glomerular filtration rate (eGFR), proteinuria, anti-human leukocyte antigen donor-specific antibody, and kidney graft biopsy histopathology) at one-year post-transplant to predict 5-year graft survival. The iBox Qualification Plan is supported by strong mechanistic and epidemiologic data of the association with late kidney functional decline and failure and includes data from single center and randomized controlled trials representing over 2,500 de novo kidney transplant recipients.

The iBox scoring system (NCT03474003), has been developed and validated in a landmark publication released in the BMJ by a team of researcher led by Pr Alexandre Loupy in Paris French NIH (Inserm), APHP and Université Paris Cité, comprising 7557 patients from 10 academic centres from Europe and the US and 3 RCT's. iBox leveraged high quality longitudinal data to build a robust predictive system for long-term kidney allograft loss. iBox has been extensively validated for use in the treatment of individual patients in the clinical care setting and common clinical scenarios including response to treatment in in T-cell mediated rejection, antibody-mediated rejection and immunosuppressive regimen minimization (BMJ 2019; 366:l4923).

The Transplant Therapeutics Consortium (TTC) is a public-private partnership founded in 2017 by the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS). This collaboration unites the transplant community, industry leaders, and regulatory agencies to foster consensus-driven, data-focused research aimed at enhancing the development of innovative tools and methods for evaluating the safety and efficacy of solid organ transplants (SOT).

This regulatory qualification achievement was accomplished by employing the resources of the TTC members and engaging with FDA throughout the biomarker qualification process. TTC is supported through funding and input from the AST*, ASTS*, argenx*, Arkana Laboratories*, Bristol Myers Squibb*, CareDx*, Critical Path Institute, CSL, CTI Clinical Trial Services, Inc.*, Eledon*, European Society of Organ Transplantation, the U.S. Food and Drug Administration (FDA), Hansa Biopharma*, HUS Helsinki University Hospital, Immucor, KU Leunven, Memo Therapeutics AG*, Natera, National Institutes of Health, Novartis, Paris Transplant Group, Pirche, Sanofi*, Takeda*, Talaris Therapeutics, Thermo Fisher Scientific, The Transplantation Society, Transplant Genomics*, University of Manitoba, and Veloxis Pharmaceuticals*.

TTC is working on its next regulatory milestone, the submission of the Full Qualification Package for regulatory endorsement of the iBox Scoring System as a reasonably likely surrogate endpoint by the FDA.

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, health care providers, academic researchers, and patient advocacy organizations, have been encouraged to work together to foster innovation in the development of new therapies by qualifying new drug development tools that can accelerate the process of making new therapies available to patients. For more information, click here. Any groups that would like to join in this effort or have information or data that may contribute to further advances, can contact JoAnn Gwynn at [email protected].

The Transplant Therapeutics Consortium (TTC) was launched in April 2017 and co-founded by the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS). TTC brings together pharmaceutical companies, diagnostic companies, academic and nonprofit partners working toward a common goal of moving the field forward toward drug development solutions in transplantation.

American Society of Transplantation 
Founded in 1982, the American Society of Transplantation (AST) is a non-profit, 501(c)3 organization dedicated to advancing the field of transplantation and improving patient care by promoting research, education, advocacy, organ donation, and service to the community through a lens of equity and inclusion. The society is the largest transplant organization in North America (consisting of nearly 5,000 professional members), representing a majority of the nation's medical professionals engaged in the field of transplantation.

Learn more at myAST.org.

American Society of Transplant Surgeons 
The American Society of Transplant Surgeons (ASTS) was founded in 1974 by 127 surgeons to unite the professionals who were advancing the fledgling field of organ transplantation. 

From this small group of dedicated individuals, we have grown to represent over 2,000 transplant professionals who are dedicated to saving and improving lives through the transformative power of organ donation and transplant surgery. Learn more about ASTS by visiting our website at ASTS.org.

*Denotes Current TTC Members

MEDIA CONTACTS:

Shauna O'Brien – AST: [email protected]

Anna Shults – ASTS: [email protected] 

SOURCE American Society of Transplantation