Duchenne Muscular Dystrophy (DMD) is a devastating neuromuscular disease that mainly affects boys. It leads to progressive muscle weakness and often ties young patients to the wheelchair at an early age. Life expectancy is 20 to 30 years on average. Treatment options for DMD are very limited. Therefore, there is a great need for transformative therapies. Roche is currently starting a registration study for the investigational drug Anti-Myostatin-Adnectin or RG6206. Currently, boys between the ages of 6 and 11 are being recruited who can still walk on their own. Promising data from animal studies and early human studies suggest that inhibition of myostatin production in children will lead to muscle growth and strengthening. The ultimate aim of the treatment is to have a positive effect on the affected children’s ability to walk and thus to lead a less dependent life.
For over one hundred years, two main tests have been used in studies in children with DMD: the 6-minute walking test (6MWT) and the 4-minute stair climbing test (4SCT). In the absence of better tests, the regulatory authorities accepted the episodic clinical outcome measures as clinical endpoints. These tests assessed the effect of investigational drugs on the gross motor parameters of DMD, such as walking and climbing stairs. Due to the inherent weaknesses, regulatory authorities such as physicians conducting clinical trials are increasingly sceptical about these endpoints.
A major problem with these tests is that they only provide a snapshot. These tests do not reflect the boy’s natural ability to move. Regulators are aware of these problems and welcome novel endpoints that complement both existing tests and capture more objective parameters of walking behaviour that are more sensitive to change.
ActiMyo, developed by the French company Sysnav, is a medical device that is worn on the ankles and measures and records walking behaviour with the highest precision. The portable activity sensor registers and characterizes parameters of walking ability such as walking speed over a longer period of time in the real environment of daily life. With the help of an algorithm that provides a meaningful interpretation of the collected data, the sensor can characterize the walking behavior in DMD and display individual changes in the gait pattern with high accuracy, independent of the boy’s motivation. This is a highly personalized approach.
ActiMyo reliably measures walking pace and motion pattern over time and is used in Roche’s Phase III program, which investigates anti-myostatin in DMD. This specific endpoint was submitted to the European Medicines Agency (EMA) for recognition as a secondary endpoint in regulatory studies.
It is the first digital endpoint involving Roche that has been recognised by a regulatory authority as being eligible for a regulatory decision. The sensitivity of the endpoint is so high that it is likely that significantly fewer patients will need to be recruited in the future to achieve the results expected from pivotal studies. In addition, the study duration will be shortened, i.e. young patients will probably have to wait less time for the potential new therapy. The fact that the EMA has now accepted this endpoint could revolutionise the development and approval of drugs for neuromuscular diseases.