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

Poster Number: 139


Douglas Sproule, MD MSc, ML Bio Solutions, Amy Harper, MD, VCU School of Medicine, Ruby Langeslay, MPH, Department of Neurology, Virginia Commonwealth University, Thulashitha Rajasingham, MSc, Bridge Bio, Hector Rodriguez, PhD, BridgeBio PharmA, Athiwat Hutchaleelaha, Ph.D., BridgeBio Pharma, ML Bio Solutions, Tricia Blankenbiller, BridgeBio Pharma, ML Bio Solutions

Introduction: Limb-girdle Muscular Dystrophy (LGMD) Type 2I, also called LGMDR9 FKRP-related, is caused by bi-allelic partial loss-of-function of the fukutin-related protein (FKRP) gene, which results in hypoglycosylation of alpha-dystroglycan (αDG). BBP-418 is an orally administered substrate supplementation intended to saturate the partially functional FKRP enzyme, driving increased glycosylation of αDG, and potentially ameliorating the root cause of LGMD2I.

Objectives: The MLB-01-003 Phase 2 study is intended to explore the safety and tolerability of BBP-418. Additionally, the feasibility and usefulness of clinical efficacy and pharmacodynamic (PD) assessments in patients with LGMD2I receiving ascending doses of BBP-418 will be investigated.

Methods: MLB-01-003 is an open label dose escalation study of patients with LGMD2I. Part 1 of the study involved three dose cohorts (6 g QD, 6 g BID and 12 g BID) treated for 3 months. During Parts 2 and 3 (ongoing OLE), all patients received 12 g BID, dose adjusted for lower weight.

Results: 14 patients with LGMD2I (aged 12-53, 8/14 homozygous for the L276I mutation) were enrolled. After 90 days of treatment, participants showed an average of +0.21 in the glycosylated αDG / total αDG ratio. A sustained reduction in Creatine kinase (CK) of >75% was observed over 12 months. Following 12+ months of treatment, increases in NSAD (0.95) and 10MWT velocity (0.09 m/s) were observed. This compares favorably to data for the same patients showing decline over the 12-month interval prior to treatment with BBP-418. BBP-418 was well-tolerated across a range of dose levels with no observed treatment-related serious adverse events, dose limiting toxicities or discontinuations. Updated data will be provided at the time of the meeting.

Conclusions: Preliminary MLB-01-003 data from patients with LGMD2I suggest a positive effect of BBP-418 on αDG glycosylation, CK, NSAD and 10MWT velocity. A global, double-blind placebo-controlled Phase 3 study is planned.