LB: Interim Analysis from Ongoing Phase 3 FORTIFY Study of BBP-418 for Patients with Limb Girdle Muscular Dystrophy 2I/R9 Meets Efficacy Endpoints

Topic:

Clinical Trials

Poster Number: 494 LBM

Author(s):

Doug Sproule, MD, BridgeBio, Katherine Mathews, MD, University of Iowa, Iowa City, Iowa, USA, Ada Lee, MD, BridgeBio Pharma Inc., Amy Rainey, BA, BridgeBio Pharma Inc., David Paul, BA, BridgeBio Pharma Inc., Tricia Blankenbiller, MS, ML Bio Solutions, Uma Sinha, PhD, BridgeBio Pharma, Thulashisha Rajasingham, PhD, BridgeBio, Tahseen Mozaffar, MD, University of California, Irvine, Volker Straub, MD, PhD, John Walton Muscular Dystrophy Research Centre, Robert Henderson, MBBS, PhD, University of Queensland, John Vissing, MD, Neurology at the University of Copenhagen

Background:

Limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) is an autosomal recessive disorder caused by pathogenic variants in the FKRP gene that impair alpha-dystroglycan (αDG) glycosylation, leading to progressive muscle weakness and cardiopulmonary decline. No approved therapies currently exist. BBP-418 is an oral, small molecule designed to restore αDG glycosylation and stabilize muscle integrity.

Methods:

FORTIFY (NCT05775848) is a randomized, double-blind, placebo-controlled, Phase 3 study evaluating the efficacy and safety of BBP-418 in individuals with LGMD2I/R9. The prespecified 1-year interim analysis assessed biochemical, functional, and safety endpoints. The primary endpoint was change from baseline in glycosylated αDG at 3 months, with key secondary endpoints including serum creatine kinase (CK), 100-meter timed test (100MTT), and forced vital capacity (FVC) at 12 months.

Results:

At the interim analysis, BBP-418 treatment showed a 1.8-fold increase in glycosylated αDG from baseline at 3 months (p<0.0001), which was sustained through 12 months (p<0.0001) versus placebo. Serum CK decreased by 82% from baseline in the BBP-418 dosed participants at 12 months. This decrease was statistically significant compared with placebo (p<0.0001). Statistically significant and clinically meaningful improvements were observed in 100MTT velocity (+0.14 m/s from baseline in BBP-treated participants; difference of 0.27 m/s in BBP-treated participants vs. placebo, p<0.0001) and FVC (+3% predicted from baseline in BBP-treated participants; difference of 5% predicted in BBP-treated participants vs. placebo, p=0.0071). BBP-418 was well tolerated with no new safety findings. Additional data from the interim analysis will be presented at the time of the meeting.

Conclusions:

The interim analysis results from the ongoing 3-year FORTIFY Phase 3 trial demonstrate that BBP-418 provides significant pharmacological and functional benefits with a favorable safety profile. These data support BBP-418 as a potential first disease-modifying therapy for LGMD2I/R9, with a favorable risk-benefit profile.