Background and Objectives: LGMD2I/R9 is a rare disease marked by progressive muscle damage in cardiac myocytes and skeletal muscle, leading to a loss of mobility. Alongside the progressive extremity weakness, symptomatic respiratory weakness and cardiac dysfunction may develop, and can be a major cause of morbidity and mortality. LGMD2I/R9 is caused by bi-allelic partial loss-of-function of the fukutin-related protein (FKRP) gene, resulting in hypoglycosylation of alpha-dystroglycan (αDG).
BBP-418 is an investigational oral therapy intended to saturate the partially functional FKRP enzyme with substrate, to drive increased glycosylation of αDG, and potentially stabilize or improve muscle function.
Results: FORTIFY (NCT05775848) is a Phase 3 multinational, double-blind placebo-controlled study that enrolled 112 individuals with genetically confirmed LGMD2I/R9. The study is being conducted at 22 sites and includes participants aged 12 to 60 years in the US, UK and Australia and 18 to 60 years in the EU. Individuals were randomized in 2:1 to receive oral BBP-418 or placebo. The study is ongoing and blinded. Demographic and study data are provided for the total population. Mean age (SD) at baseline was 35.8 (12.22) years. Fifteen participants were 12-18 years, and 97 were 18-60 years. Fifty-three percent of participants are female. The study population includes 73.1% participants with the common mutation c.826C>A.
The primary endpoint is change in North Star assessment for LGMDs from baseline in BBP-418-treated individuals relative to placebo at 36 months.
Conclusion: FORTIFY is a Phase 3 study that assesses the efficacy and safety of BBP-418 in LGMD2I/R9. Here, for the first time, we present the baseline characteristics from participants enrolled. In addition to evaluating the effect of BBP-418 on motor performance using the NSAD, the effect of BBP-418 treatment on glycosylated αDG, the hallmark of disease at the molecular level, will be investigated at 12 months as a surrogate endpoint to support accelerated approval.