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Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder that is often associated with extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) due to its impaired clearance from the circulation. Individuals with HoFH also experience increased cardiovascular events and premature mortality. Evinacumab, a fully human monoclonal antibody against angiopoietin-like 3, has demonstrated approximately 50% reductions in LDL-C levels in patients with HoFH independent of residual LDL receptor function compared to placebo. This post-hoc analysis was conducted to assess the effect of evinacumab on the change in apheresis eligibility based on the predefined US apheresis criteria in patients with HoFH. This is an ongoing, single-arm, open-label, phase 3 study (NCT03409744) that enrolled and treated patients with HoFH aged ≥12 years. All evaluable patients (n=106) received intravenous evinacumab 15 mg/kg every 4 weeks. At baseline, 67.9% (72/106) of patients qualified for apheresis and 32.1% (34/106) of patients did not qualify for apheresis using US criteria (LDL-C ≥300 mg/dL or LDL-C ≥100 mg/dL with coronary heart disease or peripheral artery disease). Overall, the mean (standard deviation) reduction in LDL-C was 130.6 (109.3) mg/dL from baseline at Week 56. Of the 72 patients who initially qualified for apheresis at baseline, over half (61.9% [39/63]) no longer qualified for apheresis following 56 weeks of treatment (data missing for 9 patients). The observed reduction in the proportion of patients qualifying for apheresis was overall maintained through to Week 184 (results not shown). Based on US apheresis eligibility criteria, treatment with evinacumab considerably reduced the proportion of patients who would qualify for apheresis. Yes Regeneron Pharmaceuticals, Inc. [ABSTRACT FROM AUTHOR]

Background: Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events., Methods/design: The COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector)., Discussion: In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response., Trial Registrations Combo I: NCT01644175 ( NCT01644175)., Combo Ii: NCT01644188 ( NCT01644188).