Abstract 17016: Trial Assessing Long-Term Use of PCSK9 Inhibition in Patients with Genetic LDL Disorders (TAUSSIG): Efficacy and Safety in Patients with Homozygous Familial Hypercholesterolemia Receiving Lipid Apheresis
Introduction: Familial hypercholesterolemia (FH) is a serious genetic disorder which causes premature cardiovascular disease due to elevated serum low-density lipoprotein cholesterol (LDL-C). Despite maximum medical therapy, many patients with homozygous FH (HoFH) also require lipid apheresis. TAUSSIG is a single-arm, open-label, treatment-only study evaluating the long-term efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in patients with severe FH not controlled on current lipid therapy. We report results from a subgroup of patients with HoFH on apheresis enrolled in TAUSSIG.
Methods: TAUSSIG eligibility criteria included age 12-80 years, clinical or genetic diagnosis of severe FH, and stable background therapy for ≥ 4 weeks. Patients on apheresis received both 420 mg evolocumab and apheresis biweekly (Q2W). Dosing frequency could be changed to 420 mg monthly after 12 weeks at investigator discretion.
Results: At the time of analysis, 24 and 13 HoFH apheresis patients had completed 12 and 24 weeks on study, respectively. All met genetic criteria for HoFH; 20 (83%) had LDL receptor mutations in both alleles. Mean baseline LDL-C was 275 mg/dL. Mean change from baseline in LDL-C was -34 mg/dL (-17%) at week 12 and -48 mg/dL (-20%) at week 24 (Table). Four patients (17%) stopped or decreased the frequency of apheresis, with mean (SE) change from baseline in LDL-C of -73 (26) mg/dL (-49%) at the time of adjustment. The 3 patients (13%) with LDL receptor negative mutations in both alleles did not have appreciable changes in LDL-C. Sixteen patients reported 85 adverse events; 84 were grade 1 or 2, one grade 3, and 1 categorized as serious. The most common adverse events were nasopharyngitis and vomiting (n = 4 each).
Conclusion: Evolocumab 420 mg Q2W reduces LDL-C in patients with HoFH receiving lipid apheresis. PCSK9 inhibition with evolocumab may be an additional therapeutic option for these patients.
Author Disclosures: E. Bruckert: Honoraria; Modest; Astra Zeneca, Merck Sharp and Dohme, Aegerion, Danone, Amgen, Novartis, Sanofi. V. Blaha: None. E.A. Stein: Consultant/Advisory Board; Modest; Amgen, Adnexus Therapeutics, Genentech, Regeneron, Sanofi, ISIS, Genzyme. F.J. Raal: Speakers Bureau; Modest; AstraZeneca, Pfizer, Merck, Amgen. Honoraria; Modest; AstraZeneca, Pfizer, Merck, Amgen, Sanofi. Consultant/Advisory Board; Modest; AstraZeneca, Pfizer, Merck. Other; Modest; Amgen, Sanofi. C.E. Kurtz: Employment; Significant; Amgen. N. Honarpour: Employment; Significant; Amgen. F. Xu: Employment; Significant; Amgen. J. Gibbs: Employment; Significant; Amgen. S.M. Wasserman: Employment; Significant; Amgen. R. Scott: Employment; Significant; Amgen. P. Couture: None.
- © 2014 by American Heart Association, Inc.