PB1046 for Dystrophic Cardiomyopathy

Dystrophinopathies are rare genetic disorders characterized by progressive muscle tissue degeneration caused by mutations in the dystrophin gene. Disease severity can range from mild to progressive muscle disorders, and includes Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy (XL-dCMP).

For people on the severe end of the spectrum, deficiency of the dystrophin protein primarily affects skeletal muscles and heart (cardiac) muscle, resulting in muscle-fiber degeneration and muscle weakness. Current exon-skipping approaches to increasing dystrophin levels focus on delaying loss of ambulation, but don’t address the cardiac issues that, based on improvements in general care, are now the leading cause of death in DMD. There are no FDA-approved therapies that treat dystrophic cardiomyopathy.

Positive pre-clinical data demonstrated that chronic administration of PB1046 in a DMD mouse model significantly slowed the deterioration of cardiac function, preserved contractility and enabled faster relaxation of the cardiac muscle. PB1046 protected against contraction-induced damage in skeletal muscles of mice, and reduced the degree of fibrosis in both cardiac and skeletal muscles.

PhaseBio continues to evaluate PB1046 in pre-clinical models of dystrophic cardiomyopathy, while exploring regulatory pathways for the indication.

PB1046 has received orphan drug designation from the FDA for the treatment of cardiomyopathy associated with dystrophinopathies.