Effects of CER-001 on carotid atherosclerosis by 3TMRI in homozygous familial hypercholesterolemia (HoFH): the modifying orphan disease evaluation (MODE) study

BACKGROUND: Patients suffering from HoFH are characterized by extreme atherosclerosis progression, leading to premature death. HDL has been shown to exert anti-atherogenic effects. We set out to investigate the effect of infusions of CER-001, an engineered pre-beta HDL mimetic, on atherosclerosis by carotid 3T MRI. METHODS: HoFH subjects, on maximally tolerated LDL lowering therapy, underwent twelve biweekly infusions of CER-001 (8 mg/kg). 3TMRI was performed at baseline and at 6 months. The primary outcome parameter was change in carotid Mean Vessel Wall Area. Secondary parameters included other MRI-derived measurements of the carotids. RESULTS: 23 subjects were enrolled in the study (6 male, 17 female, aged 39 ± 14 years). Results for carotid wall measurements in the 18 subjects who qualified for the modified intent-to-treat analyses are shown in the table (not attached). CONCLUSION: CER-001 infusions significantly reduced both carotid Mean Vessel Wall Area and Volume in subjects with HoFH over a six-month treatment period, indicating that HDL therapy is complementary to LDL-c-lowering treatment. CER-001 may represent a new therapy for addressing the unmet medical need in HoFH patients.