Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

• AKCEA-ANGPTL3-LRX (Drug), also known as ISIS 703802: Single open-label cohort

Primary outcomes

• Reduction of low density lipoprotein cholesterol (LDL-C). [14 weeks]: Percent change in LDL-C from Baseline to week 14.

Secondary outcomes

• Effect of ISIS 703802 on plasma angiopoietin like 3 (ANGPTL3). [7 and 14 Weeks]: Absolute and percentage change in ANGPTL3 protein from Baseline to Week 14 will be summarized.
• Effect of ISIS 703802 on lipid parameters. [7 and 14 Weeks]: Absolute and percentage change from Baseline to Week 14 will be summarized.
• Evaluate plasma trough levels of ISIS 703802. [14 Weeks]: Plasma trough levels of ISIS 703802 during treatment period and those during post-treatment follow up period will be descriptively summarized.
• The safety of ISIS 703802 by the incidence of treatment-emergent adverse events [14 Weeks]: The safety of ISIS 703802 will be assessed by determining adverse effects.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Body mass index (BMI) ≤ 35 kg/m2,
* Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus OR an untreated LDL-C > 500 mg/dL (13 mmol/L) or treated LDL-C ≥ 300 mg/dL (2.59 mmol/L) together with either cutaneous or tendon xanthoma before age 10 years OR familial medical history of genetically confirmed heterozygous FH in both parents OR untreated elevated LDL-C and TC > 250 mg/dL consistent with the disease,
* Patients must be on stable LDL-C lowering agents or on regular apheresis

Exclusion Criteria:

* Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to Screening, or cerebrovascular accident within 24 weeks prior to Screening.
* Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%