BridgeBio Reports Positive Phase 3 Results for Limb Girdle Muscular Dystrophy Therapy

Rare Daily Staff

BridgeBio Pharma reported positive top-line results from its phase 3 pivotal study of BBP-418, an experimental small-molecule therapy for people living with limb-girdle muscular dystrophy type 2I/R9.

People with a specific FKRP gene mutation, L276I, often begin to show symptoms in late childhood. As adults, about one in four lose the ability to walk independently, around one in ten need breathing support, and about one in three develop weakening of the heart muscle (cardiomyopathy), which worsens gradually over time. Those with other FKRP mutations generally become affected earlier, often in early childhood. Their symptoms progress more quickly, leading to loss of walking ability by age 20, heart problems in most cases, and severe breathing weakness by around age 30.

BBP-418 is an experimental oral therapy designed to supply supraphysiological levels of the substrate used by FKRP during glycosylation of alpha-dystroglycan. If approved, BBP-418 has the potential to be the first disease-modifying oral therapy available for people with limb-girdle muscular dystrophy type 2I/R9.

Limb-girdle muscular dystrophy type 2I, also called R9, is a rare inherited muscle disease caused by a mutation in the FKRP gene. This gene helps make a protein that stabilizes muscle cells. When the FKRP gene does not work correctly, the body loses part of its ability to add sugars to another protein (alpha-dystroglycan), which protects muscle fibers. As a result, muscles gradually weaken and break down over time. The disease usually starts by affecting the muscles of the hips and thighs, then spreads to the shoulders, arms, and eventually the heart and breathing muscles.

BBP-418 has previously received Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration, and Orphan Drug designation from the European Medicines Agency. Consistent with the Rare Pediatric Disease designation from the FDA, if BBP-418 is approved, BridgeBio may qualify for a Priority Review Voucher.

The planned interim analysis at 12 months from the phase 3 FORTIFY study showed a highly statistically significant increase of 1.8 times change from baseline, from 22.7 percent of control at baseline to 39.6 percent of control at three months, in the primary interim analysis endpoint of glycosylated alpha-dystroglycan (αDG) observed in the BBP-418-treated group, compared to approximately no change in the placebo group.

BBP-418-treated individuals had statistically significant, clinically meaningful improvements at 12 months in all key clinical endpoints studied. BBP-418 was well tolerated, with no new or unexpected safety findings observed.

The company said it intends to engage the FDA later this year to discuss these data and plans for submission in the first half of 2026 for approval to market BBP-418.

Substantial and highly statistically significant increases in glycosylated αDG were observed both in individuals with the L276I homozygous genotype and other FKRP genotypes.

“The FORTIFY results reaffirm the power of targeting this genetic disease at its source with relentless focus and compassion,” said Douglas Sproule, chief medical officer of ML Bio Solutions, a BridgeBio company developing BBP-418 for LGMD2I/R9. “For individuals living with LGMD2I/R9, a condition that slowly takes away the strength, breathing, and independence of an individual, each day matters.”

Photo: Douglas Sproule, chief medical officer of ML Bio Solutions