Preliminary Results from MLB-01-003: An Open Label Phase 2 Study of BBP-418 in Patients with Limb Girdle Muscular Dystrophy Type 2I

Clinical Trials
Amy Harper, MD, VCU
Ruby Langeslay, MPH, VCU
Hector Rodriguez, PhD, BridgeBio Pharma
Athiwat Hutchaleelaha, PhD, BridgeBio Pharma
Karen Kelley, ML Bio Solutions
Doug Sproule, MD, MSc, ML Bio Solutions

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.