BridgeBio Pharma has posted an upbeat update on its limb-girdle muscular dystrophy type 2i (LGMD2i) program. With a phase 2 trial linking BBP-418 to positive biomarker changes, BridgeBio is preparing to talk to regulators about paths to market for the treatment of muscle wasting in the arms and legs.
The phase 2 study enrolled 14 ambulatory and non-ambulatory patients with LGMD2i. Across three cohorts, BridgeBio tested ascending doses of the oral drug candidate BBP-418 to determine the effects of providing the FKRP enzyme with precursor sugar molecules to bypass the metabolic defect in LGMD2i. The study assessed participants at days 90 and 180.
BridgeBio saw a 43% increase in the ratio of glycosylated alpha-dystroglycan (αDG) to total αDG from baseline across all three dosing cohorts. The result points to the potential for BBP-418 to address the root cause of LGMD2i.
After 90 days of treatment, BridgeBio saw an average of 70% reduction in creatine kinase (CK), a marker of muscle breakdown. An average 77% reduction was seen in the first two cohorts after 180 days. Eleven of 12 participants had at least a 50% reduction in CK. Three-quarters of participants reached twice the normal range. The data point to a possible reduction in muscle breakdown.
“The positive results from the phase 2 study exceed expectations and are incredibly exciting as they demonstrate consistent improvements in key markers of muscle function and support further study,” Amy Harper, M.D., a professor in the department of neurology at Virginia Commonwealth University and primary investigator of the phase 2 clinical trial, said in a statement.
BridgeBio has an early sign that the biomarker changes translate into improvements in clinical outcomes. Participants experienced a 3% increase in velocity in the 10-meter walk test (10MWT) at Day 90, and a 4% increase at Day 180. The participants’ 10MWT velocity declined over the six months before the start of the trial.
With investigators seeing no treatment-related serious adverse events, dose limiting toxicities or discontinuations, BridgeBio thinks the data support further development of BBP-418. A phase 3 clinical trial is scheduled to start in the second half of the year, and BridgeBio plans to talk to regulatory agencies this year about potential paths to market.