Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neuron leading to weakness and death often resulting from failure of the respiratory muscles. There have been numerous recent discoveries in ALS research leading to potential therapies that will need testing in clinical trials. Due to limitations of traditional outcome measures, trials require large sample sizes, long durations. Recently, a pivotal ALS trial fails to meet its primary target and researchers attribute it to the endpoint selection rather to the drug product.
Digital biomarkers collected with wearable devices provide an objective assessment performed in real-life and offer powerful alternatives to traditional outcome. SV95C is the first digital outcome measure qualified by EMA for ambulant patients living with Duchenne Muscular Disease. It demonstrates that digital outcome can measure remotely and reliably motor function and have the potential to enable shorter trials with less patients.
We designed a longitudinal natural history study in ALS and tested several candidate digital outcome measures. Participants were assessed with standard evaluations including the amyotrophic lateral sclerosis functional rating scale, six-minute walk test, Medical Research Council scores, Ashworth score, hand dynamometer, pulmonary function and cognitive tests every 3 months for 1 year. After each visit, patients were asked to wear for one month one inertial sensor at the ankle and one at the wrist for continuous assessment of motor function in real-life. These data will be compared with already acquired normative data. At the present time, 11 patients with ALS (3 females, 8 males) aged from 44 to 72 years old were included. Four patients discontinued the study due to death or permanent ventilation.
We will present performance of the candidate digital outcome measures and compare the most robust digital measure to traditional outcome to test its capability to enable more efficient trials.