The Problem

Duchenne Muscular Dystrophy (DMD) is a fatal disease caused by a genetic mutation in the DMD gene and manifests as progressive muscle degeneration leading to loss of ambulation, loss of upper limb function, respiratory and cardiac function failure. A major hurdle when it comes to improving treatments for DMD is the complexity of the disease itself, including the wide variety of genetic mutations. This complexity means that developing effective treatments can be difficult, as researchers must consider multiple factors, such as the specific type of mutation, disease stage and age of individuals living with DMD. 

Variable disease progression, and lack of standardized indicators of disease for DMD are also major challenges which can make it difficult to assess treatment effectiveness. 

In addition, the rarity of the disease poses a challenge for clinical trials. DMD has approximately 20,000 new diagnoses per year, mostly in boys. The growing number of drugs in development, and the small population size, makes it difficult to recruit enough patients for clinical trials, which can lead to long trial durations and limited statistical power. In turn, this makes it difficult to detect treatment effects. 

The Solution

To combat these challenges, the Duchenne Regulatory Science Consortium (D-RSC) has created an integrated database of patient-level clinical data from DMD studies, which is partially available for analysis by the Duchenne community as permitted by the owners of each dataset. Created by Critical Path Institute (C-Path) and Parent Project Muscular Dystrophy (PPMD), D-RSC has generated  standard terminology to integrate data and has written the CDISC Duchenne Muscular Dystrophy Therapeutic Area User Guide, which is available to the community. Using its reach database, D-RSC has completed the development of the first Clinical Trial Simulation tool for DMD and recently received a Letter of Support from the EMA while additional regulatory review processes are ongoing.  

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 Impact

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