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 DMD, BMD and X-linked dilated cardiomyopathy (XL-dCMP).
For people at 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. Patients usually develop cardiomyopathy in adolescence and, due to improvements in general care, cardiomyopathy is now the leading cause of death in DMD, BMD and XL-dCMP patients.
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.
There are currently no approved therapies for dystrophic cardiomyopathy, creating an unmet need for treatments that complement those focused on slowing disease progression. We are evaluating the regulatory pathway for PB1046 in dystrophic cardiomyopathy, including DMD-related cardiomyopathy and BMD-related cardiomyopathy, and plan to initiate a phase 2 study in DMD patients by early 2018.
PB1046 has received orphan drug designation from the FDA for the treatment of cardiomyopathy associated with dystrophinopathies.