Duchenne Regulatory Science Consortium

Duchenne Muscular Dystrophy (DMD) is a life-threatening disease caused by a genetic mutation in the DMD gene, leading to loss of ambulation, loss of upper limb function, and respiratory and cardiac failure.

A major hurdle in improving treatments for DMD is the disease’s complexity, including its wide variety of genetic mutations. Researchers must consider factors such as the specific mutation type, disease stage, and patient age. Additionally, variable disease progression and the lack of standardized indicators complicate treatment assessment.

The rarity of DMD, with approximately 20,000 new diagnoses per year, mostly in boys, further challenges clinical trials. The small patient population and the growing number of drugs in development make it difficult to recruit enough participants, leading to long trial durations and limited statistical power, which hinders the detection of treatment effects.

In collaboration with C-Path’s Predictive Safety Testing Consortium, we are developing glutamate dehydrogenase (GLDH) as a safety biomarker for liver toxicity in patients with underlying muscle damage and have received a formal “letter of support” from EMA and positive response to the Qualification Plan for GLDH from the FDA. Future projects may include supporting the regulatory acceptance of other DMD-relevant biomarkers and patient reported outcomes or development of additional models to be leveraged for drug development.

The D-RSC team works every day to mitigate the effects of DMD and to bring new treatments to market faster. To do so, D-RSC provides:

The development of disease progression models of five endpoints to integrate into a quantitative solution – a Clinical Trial Simulation (CTS) tool

Qualification of glutamate dehydrogenase as a liver safety biomarker in trials involving patients affected by muscle disorders.

Regulatory acceptance of Clinical Outcome Assessments (COAs) for DMD

Regulatory acceptance of quantitative tools based on MRI biomarkers for DMD and their relationship to disease progression

Models of additional endpoints as data become available

• 2018: EMA Letter of Support for glutamate dehydrogenase, a biomarker of hepatocellular liver injury: in collaboration with the Predictive Safety Testing Consortium (PSTC) at C-Path 
• 2020: FDA accepted Letter of Intent submitted in collaboration with PSTC for clinical qualification of four skeletal muscle injury biomarkers (TNNI2, MYL3, FABP-3, CK-MM) 
• 2021: Led a Type B meeting with the FDA to discuss Master protocol development of a Master Protocol for the Duchenne Adaptive Platform Trial 
• 2022: EMA Letter of support on “A model-based clinical trial simulation tool to optimize clinical trial design of studies to investigate efficacy of potential therapies for Duchenne muscular dystrophy”  
• 2023: Submitted final briefing package to FDA for endorsement of two model based clinical trial simulation tools under the Fit-for-Purpose Initiative   
• 2024: Submitted response to two FDA Information Request letters on the final briefing package under review for endorsement of two model based clinical trial simulation tools under the Fit-for-Purpose Initiative   

• Published paper on “A Computational Tool to Optimize Clinical Trial Parameter Selection in Duchenne Muscular Dystrophy: A Practical Guide and Case Studies” (2024).   
• Published paper on “A model-informed clinical trial simulation tool with a graphical user interface for Duchenne muscular dystrophy” (2024).
• Published protocol entitled “A systematic review of the body of evidence for the use of protein biomarkers of muscular damage and disease progression in Duchenne and Becker Muscular Dystrophy” in PROSPERO (2024). 
• Published CDISC Duchenne Muscular Dystrophy Therapeutic Area User Guide v1.0 – Cardiac Imaging Supplement (2024). 
• Published paper on “Transforming Drug Development for Neurological Disorders: Proceedings from a Multidisease Area Workshop” (2023).
• Published paper on “Multivariate modeling of magnetic resonance biomarkers and clinical outcome measures for Duchenne muscular dystrophy clinical trials” (2023).
• Published paper on “Development of a model-based clinical trial simulation platform to optimize the design of clinical trials for Duchenne muscular dystrophy” (2021).
• Published paper on “Standardized Data Structures in Rare Diseases: CDISC User Guides for Duchenne Muscular Dystrophy” (2020).
• Published paper on “Serum Glutamate Dehydrogenase Activity Enables Early Detection of Liver Injury in Subjects with Underlying Muscle Impairments” in partnership with the Predictive Safety Testing Consortium (2020).
• Published paper on “Seeking a Better Landscape for Therapy Development in Neuromuscular Disorders” (2018).
• Published CDISC Duchenne Muscular Dystrophy Therapeutic Area User Guide Version 1.0 (2017).

• Critical Path Institute
• Parent Project Muscular Dystrophy

• CureDuchenne

• Binghamton University
• Children’s Hospital of Philadelphia
• Children’s National Health System
• Children’s National Heart Institute
• Cincinnati Children’s Hospital Medical Center
• Hadassah Medical Center
• Icahn School of Medicine at Mount Sinai
• Indiana University School of Medicine
• KTH–Royal Institute of Technology
• Leiden University Medical Center
• Nationwide Children’s Hospital
• Oregon Health & Science University
• Paris Cité University
• Stanford University
• UH Rainbow Babies and Children’s Hospital
• UMass Memorial
• University of Arizona
• University of California, Davis
• University of Florida
• University of Leicester, UK
• University of Messina, Italy
• University of Oxford
• Vanderbilt University Medical Center

• Mindy Cameron, AdvocacyWorks
• Ryan Russell, Life on Positivity
• Adith Thummalapalli, Parent Project Muscular Dystrophy
• Colin Werth, Parent Project Muscular Dystrophy

• Pavel Balabanov, EMA
• Atul Bhattaram, FDA
• Michelle Campbell, FDA
• Emily Freilich, FDA
• Ami Mankodi, FDA
• Veneeta Tandon, FDA
• Emily Carifi, NIH/NIAMS