BridgeBio Unveils Strong Phase 3 Interim Data for BBP-418 in LGMD2I/R9 at MDA Conference

BridgeBio Pharma, Inc.a biopharmaceutical company targeting genetic diseases, presented compelling interim results from the Phase 3 FORTIFY trial (NCT05775848) of oral BBP-418 in patients with limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9).

Delivered as a late-breaking oral presentation by Katherine Mathews, M.D., Professor of Pediatrics and Neurology at the University of Iowa, the data highlight BBP-418’s potential as the first therapy for this progressive, untreated condition with early-onset motor loss.

At 12 months, treatment with BBP-418 led to a rapid and sustained reduction in serum creatine kinase (CK), a marker of muscle damage. Nearly 60% of treated patients achieved CK levels within two times the upper limit of normal, while 38.3% reached normal CK levels.

The therapy also demonstrated improvements in mobility. Patients receiving BBP-418 completed the 100-meter timed test (100MTT) about 31 seconds faster than placebo at 12 months. On the 10-meter walk test, walking speed improved by 0.13 m/s, while the placebo group experienced a decline.

Commenting on the findings, Katherine Mathews, MD, said patients with LGMD2I/R9 currently have no disease-specific treatments and the condition progresses to significant loss of motor function. She noted that early separation from placebo in the 100-meter timed test suggests a rapid treatment effect, and the improvements in motor and pulmonary function along with a favorable safety profile indicate BBP-418 may offer meaningful clinical benefit.

BBP-418 was generally well tolerated, with a safety profile comparable to placebo. Serious adverse events were reported in 5.4% of BBP-418 patients versus 7.9% in the placebo group, and no treatment-related serious adverse events or deaths were reported.

BridgeBio plans to submit a New Drug Application (NDA) to the FDA in the first half of 2026. If approved, BBP-418 could become the first therapy for LGMD2I/R9 and potentially the first approved treatment for any form of limb-girdle muscular dystrophy, with a potential U.S. launch expected in late 2026 or early 2027.

LGMD2I/R9 is a rare inherited muscle disorder caused by mutations in the FKRP gene. The disease primarily affects the muscles around the hips and shoulders, leading to progressive muscle weakness, difficulty walking, and eventual loss of mobility. Many patients also develop respiratory or heart complications over time. There are currently no disease-specific approved treatments for this condition.

BBP-418 is an oral small-molecule therapy designed to address the underlying metabolic defect in LGMD2I/R9 caused by mutations in the FKRP gene, which impair the glycosylation of alpha-dystroglycan (αDG), a protein that stabilizes muscle cells and protects them from damage during contraction. BBP-418 provides ribitol, a precursor molecule that helps restore proper glycosylation of αDG by supporting residual FKRP enzyme activity. By increasing αDG glycosylation, the therapy aims to improve muscle cell stability and reduce progressive muscle damage.

Reference

BBP-418 Demonstrates Consistent E cacy and Favorable Safety Pro le in Phase 3 FORTIFY Interim Analysis in LGMD2I/R9, 11 March 2026, BBP-418-Demonstrates-Consistent-Efficacy-and-Favorable-Safety-Profile-in-Phase-3-FORTIFY-Interim-Analysis-in-LGMD2IR9-2026.pdf

Study of LGMD2i therapy BBP-418 exceeds interim analysis enrolment, 25 June 2024, Muscular Dystrophy, https://musculardystrophynews.com/news/phase-3-trial-lgmd2i-treatment-bbp-418-exceeds-interim-analysis-enrollment

Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients with Limb Girdle Muscular Dystrophy 2I (LGMD2I) (Fortify), ClinicalTrials.gov ID NCT05775848, https://clinicaltrials.gov/study/NCT05775848