Introduction: Limb Girdle Muscular Dystrophy (LGMD) Type 2I, also called LGMDR9 FKRP-related, is caused by bi-allelic loss-of-function of the fukutin-related protein (FKRP) gene which results in hypoglycosylation of alpha-dystroglycan (?DG). BBP-418 (ribitol) is an orally administered substrate supplementation intended to saturate the FKRP enzyme driving increased glycosylation of ?DG, thus ameliorating the root cause of disease in LGMD2I.
Objectives: The MLB-01-003 Phase 2 study is intended to explore the safety and tolerability, feasibility and usefulness of selected clinical efficacy and pharmacodynamic (PD) assessments in patients with LGMD2I receiving ascending doses of BBP-418.
Methods: This is an open label study in ambulatory and non-ambulatory patients with LGMD2I conducted at Virginia Commonwealth University. Part 1 of the study involved three ascending dose cohorts treated for 3 months with BBP-418: cohort 1 (n=4, dose 6 g daily), cohort 2 (n=4, dose 6 g twice daily) and cohort 3 (n=6, dose 12 g twice daily). During Part 2 of the study, all patients received 12 g twice daily (weight adjusted for lower weight patients) for 3 months.
Results: 14 patients with LGMD2I were enrolled in the study. Amongst the first 12 study participants for whom data is available (n=12, aged 12-53), 8/12 were homozygous for the common mutation. 9/12 were ambulatory (able to complete the 10 m walk test in <12 seconds). All 12 patients showed declines in creatine kinase (CK) (mean ~70% decrease) from baseline assessment after 3 months of treatment with BBP-418 in Part 1. No drug-related SAEs have occurred. Additional updated safety, laboratory and clinical data may be provided at the time of the meeting.
Conclusions: Preliminary MLB-01-003 data from patients with LGMD2i treated with BBP-418 suggests a positive effect on CK, a widely used biomarker of muscle injury. A larger, global, double-blind placebo-controlled phase 3 study is planned for 2022.