A Long-term Follow-up Study to Evaluate the Safety and Efficacy of RGX-501

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by absent or severely reduced capacity to catabolize circulating LDL particles by the hepatic LDL receptor. As a consequence, HoFH subjects present abnormal total plasma cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. Early initiation of aggressive treatment for these patients is therefore essential. Unfortunately, despite existing therapies, treated LDL-C levels could remain well above acceptable levels. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy, RGX-501, may be a viable approach to treat this disease and improve response to current lipid-lowering treatments.

This is a prospective, observational study to evaluate the long-term safety and efficacy after a single administration of RGX-501. Eligible participants are those who previously have enrolled in a clinical study and received a single intravenous infusion of RGX-501.

• Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy (Drug), also known as RGX-501: No investigational product will be administered in this study. All participants have previously received a one-time intravenous infusion of RGX-501 in a separate clinical trial

Primary outcomes

• Number of incidents of new and unexpected adverse events and serious adverse events. [Up to 5 years after receiving treatment with RGX-501]: The number of times a new and unexpected adverse event and/or serious adverse event is reported.

Secondary outcomes

• The absolute LDL-C level in mg/dL by beta quantification [Year 3 after receiving treatment with RGX-501]: Absolute LDL-C level by beta quantification at Year 3 after receiving treatment with RGX-501
• Absolute total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), calculated non-HDL-C, triglycerides (TG), and lipoprotein a (Lp(a)) over the study duration [Up to 5 years after receiving treatment with RGX-501]: Absolute total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), calculated non-HDL-C, triglycerides (TG), and lipoprotein a (Lp(a)) over the study duration
• Usage of lipid-lowering therapies over time [Up to 5 years after receiving treatment with RGX-501]: Usage of lipid-lowering therapies over time

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* To be eligible to participate in this study, a participant must have previously received RGX-501 in a separate parent trial, and the participant or participant's legal guardian(s) is/(are) willing and able to provide written, signed informed consent after the nature of the study has been explained, prior to any research-related procedures.

Exclusion Criteria:

* None