FORTIFY: A Phase 3 Study to Evaluate Efficacy & Safety of BBP-418 in Individuals With Limb Girdle Muscular Dystrophy 2I (LGMD2I), LGMDR9 FKRP-Related

Topic:

Clinical Trials

Poster Number: T370

Author(s):

Divya B. Reddy, MD, ML Bio Solutions, a BridgeBio company, David E. Weinstein, MD, PhD, ML Bio Solutions, Tricia Blankenbiller, MS, ML Bio Solutions, a BridgeBio company, Amy Rainey, ML Bio Solutions, a BridgeBio company, Lindsay Reklis, ML Bio Solutions, a BridgeBio company, Douglas Sproule, MD, MSc, ML Bio Solutions, a BridgeBio company

Introduction: 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) and progressive muscle damage. BBP-418 is an oral substrate supplementation intended to saturate the partially functional FKRP enzyme, driving increased glycosylation of αDG, and potentially stabilizing or improving muscle integrity.

In an ongoing open-label Phase 2 study in 14 individuals with LGMD2I/R9, BBP-418 was well-tolerated. Following 21+ months of dosing, stabilization in measures of ambulation (10MWT, 100mTT) and motor performance (NSAD) was observed. Marked increases in glycosylated αDG and reductions in serum CK were initially noted at 3 months post-dosing and sustained over 21 months.

Based on these promising data, a Phase 3 study was designed to further assess the safety, tolerability, and efficacy of BBP-418 in LGMD2I/R9.

Methods: FORTIFY (NCT05775848) is a Phase 3 multinational, multicenter, double-blind study enrolling ~81 individuals with genetically confirmed LGMD2I/R9, aged 12 to 60 years. Individuals will be randomized in a 2:1 ratio to receive oral BBP-418 or placebo.

The primary endpoint will be change in NSAD from baseline in BBP-418-treated individuals relative to placebo at 36 months. To evaluate PROs, items from the PROMIS Pediatric and Adult Physical Function Item Banks were selected to create custom disease specific Physical Function PROMIS questionnaires. An interim analysis of ~42 individuals with LGMD2I/R9 will evaluate glycosylated αDG levels, FVC, 100mTT, and PROs at 12 months.

Conclusion: FORTIFY is a Phase 3 randomized, placebo-controlled study that will assess the safety, tolerability, and efficacy of BBP-418 in LGMD2I/R9. In addition to evaluating the effect of BBP-418 on motor performance using the NSAD, the effect of BBP-418 treatment on glycosylated αDG levels, the hallmark of disease at the molecular level, will be investigated at 12 months with potential to use this biomarker as a surrogate endpoint in LGMD2I/R9.