A Retrospective, Multicenter, International Study to Characterize the Natural History of Danon Disease

Danon disease (DD) is a rare X-linked dominant genetic disorder characterized by cardiomyopathy, skeletal myopathy, and neurocognitive deficits. The disease is caused by a mutation in the lysosome associated membrane protein-2 gene (LAMP2). LAMP2 functions as a lysosomal membrane receptor in autophagy. Most men and many women with LAMP2 gene mutations will develop cardiac disease that includes hypertrophic cardiomyopathy and/or dilated cardiomyopathy, cardiac pre-excitation syndrome, and a propensity for arrhythmias. The prognosis is directly related to the severity of the cardiac disease, and many patients will die from sudden cardiac death. Males are typically more severely affected than females.

There is currently no therapy available to cure, or even prevent disease progression. DD treatment is thus primarily supportive therapy, and survival beyond 25 years without a cardiac transplantation is improbable for afflicted male patients.

Rocket Pharmaceuticals, a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare pediatric disorders, is developing Rocket Pharmaceuticals Adeno-associated- vector-501 (RP-A501) (AAV9.LAMP2B), an investigational gene therapy product for DD and the first potential gene therapy for monogenic heart failure.

This retrospective, multicenter, international, longitudinal, non- interventional study of DD patients with confirmed LAMP2 mutation aims at characterizing the Natural History of disease in males and females. The Real-world data collected from patients in this natural history study will help support the overall development and protocol design of the RP-A501 gene therapy pivotal trial to be submitted to the health authorities.

Additionally, this study will allow identification of the core centers managing DD patients in several countries as well as the description of the disease characteristics, diagnosis pathway and disease progression. This will inform the development of patient profiles for future studies, including a potential prospective observational study to investigate the burden of disease among DD patients and an international patient registry for Danon disease.