BridgeBio’s BBP-418 showed cardiac biomarker normalization and favorable functional findings at 12 months in the Phase 3 FORTIFY trial for LGMD2I/R9.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
BridgeBio Pharma has reported new exploratory cardiac findings from the 12-month interim analysis of the Phase 3 FORTIFY trial (NCT05775848) evaluating oral BBP-418 in individuals with limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), an FKRP-related genetic muscular dystrophy.
At baseline, 25 of 109 participants had elevated high-sensitivity troponin I (HS troponin I), a biomarker associated with cardiac muscle injury. Among evaluable participants with elevated baseline levels, 100% of those receiving BBP-418 had HS troponin I within the normal range at Month 12, compared with 40% receiving placebo (p=0.0248).
HS troponin I also declined more with BBP-418 than placebo, with a least-squares mean difference of −17.8 ng/L (95% CI, −35.1 to −0.5; p=0.0443).
Cardiac function showed a favorable finding as well. At Month 12, 54% of participants receiving BBP-418 had stable or improved left ventricular ejection fraction (LVEF), compared with 25% receiving placebo (p=0.0262). At baseline, 18 of 105 participants had LVEF below 50%.
The cardiac analyses were exploratory, non-alpha-controlled, and based on relatively small patient subsets. Both HS troponin I and LVEF will continue to be monitored in FORTIFY.
BBP-418 Targets the FKRP Pathway
LGMD2I/R9 is caused by partial loss-of-function mutations in the fukutin-related protein (FKRP) gene. FKRP contributes to glycosylation of alpha-dystroglycan (αDG), a protein involved in maintaining muscle-cell stability.
BBP-418 is an investigational oral glycosylation substrate therapy designed to provide additional substrate to partially functional FKRP enzyme, with the aim of increasing αDG glycosylation and potentially improving muscle function.
Separate data from the 2026 World Muscle Society Congress showed that glycosylated αDG was significantly reduced in 34 asymptomatic heterozygous FKRP carriers compared with healthy controls. Within FORTIFY, BBP-418 increased mean glycosylated αDG to levels observed in asymptomatic carriers by Month 3, with the increase sustained through Month 12. Levels were reported above carrier levels at Month 12.
Functional and Safety Findings
The 12-month interim analysis also showed favorable trends in functional measures, including the 10-meter walk test and 100-meter timed test, with treated participants improving while placebo recipients declined across key measures. BridgeBio also reported that 38% of patients achieved normal creatine kinase levels.
The 12-month analysis assessed glycosylated αDG as a potential surrogate endpoint to support an accelerated-approval pathway. This is distinct from FORTIFY’s primary clinical endpoint, which is change from baseline in the North Star Assessment for Limb-Girdle Muscular Dystrophies (NSAD) at 36 months.
BBP-418 continued to demonstrate a favorable safety and tolerability profile. Treatment-emergent adverse events were reported at rates comparable with placebo, with no treatment-related serious adverse events or new or unexpected safety findings reported.
Regulatory Status and Next Steps
BBP-418 is under FDA Priority Review, with a PDUFA target action date of November 27, 2026. The therapy has received FDA Orphan Drug, Fast Track, and Rare Pediatric Disease Designations, as well as EMA Orphan Drug Designation.
If approved, BBP-418 could become the first approved therapy for LGMD2I/R9. BridgeBio plans to initiate studies in children younger than 12 years with LGMD2I/R9 in the first half of 2027 and evaluate the therapy in LGMD2M/R13 and LGMD2U/R20.
What the Data Mean
The 12-month findings provide evidence of biological activity across cardiac, skeletal-muscle, biomarker, and functional measures. However, the exploratory cardiac analyses and biomarker changes do not establish long-term clinical benefit or disease modification.
Longer-term FORTIFY results, particularly the 36-month NSAD assessment, will be important in determining whether the biological effects observed with BBP-418 translate into durable functional benefit and meaningful disease modification in LGMD2I/R9.
Reference
BBP-418 Demonstrates Potential to Be Disease Modifying Therapy, Restoring Cardiac and Disease Markers to Unaffected Levels, BridgeBio Pharma, October 5, 2026
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
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.