EP.87MYODA clinical program: composite score for assessing the efficacy of BIO101 (MAS activator) in ambulatory and non-ambulatory Duchenne boys

Abstract

The purpose of the clinical program MYODA is to evaluate muscle strength and function in boys suffering from Duchenne Muscular Dystrophy (DMD) under long-term oral administration of BIO101 (20-hydroxyecdysone, MAS activator). Ambulant and non-ambulant DMD boys will be recruited. The heterogeneity of the clinical course of DMD has long been recognised and more recently has been captured in registry studies (Ricotti et al. 2013, 2016, Mercuri et al. 2016). Moreover, the mode of action of BIO101 and the pre-clinical proof-of-concept (PoC) suggest that DMD patients who will benefit from BIO101 is quite broad and that this benefit can be shown in a variety of functions: mobility, strength and respiratory. Due to study size limitation, using multiple outcomes and studies to assess totality of evidence for efficacy and safety is desirable for rare disease drug development. In comparing a new treatment with a control for DMD under a randomized clinical trial setting, each study patient has multiple efficacy outcomes collected over time (NSAA, PUL, 6MWT, MyoPinch, MyoGrip, PEF, FVC). Instead of defining a primary endpoint using a single outcome and identifying several secondary endpoints like most conventional studies, Biophytis presents several approaches to utilize multiple outcomes simultaneously to evaluate BIO101 effect. The resulting procedures should be more powerful to detect the treatment difference than the conventional design and also provide clinically meaningful interpretation on the totality of treatment efficacy evidence (Ricotti et al.2019). Biophytis hypothesizes that a composite score, which covers both muscle strength, skeletal muscle and respiratory functions and captures changes across the loss of ambulation might be best adapted to detect changes across the wide disease spectrum. Biophytis will study how the change in the endpoint may be clinically meaningful. Biophytis will extend the analysis using Matching population from DMD databases.