Anti-PCSK9 Monotherapy for Hypercholesterolemia

Abstract

In the largest monotherapy trial using a PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 [MENDEL-2]; NCT01763827).

Evaluation of Evolocumab (AMG 145), a Fully Human Anti‐PCSK9 IgG2 Monoclonal Antibody, in Subjects With Hepatic Impairment

“…Safety and tolerability profiles in the present study were consistent with previous studies of evolocumab6, 7, 8, 9, 10 and did not identify any risks. No anti‐evolocumab antibodies were detected in any participant.…”

“…The timing and magnitude of LDL‐C lowering after a dose of evolocumab were consistent with those seen in other studies in patients and healthy volunteers 5, 6, 8, 17, 31. For example, the randomized, double‐blind, placebo‐controlled, phase 2 MENDEL study showed that monotherapy with evolocumab 140 mg Q2W in 45 patients with hypercholesterolemia (baseline LDL‐C 3.6 mmol/L) reduced LDL‐C from baseline by 51% (95% CI –56% to –46%) after 12 weeks of treatment 31.…”

“…For example, the randomized, double‐blind, placebo‐controlled, phase 2 MENDEL study showed that monotherapy with evolocumab 140 mg Q2W in 45 patients with hypercholesterolemia (baseline LDL‐C 3.6 mmol/L) reduced LDL‐C from baseline by 51% (95% CI –56% to –46%) after 12 weeks of treatment 31. Similarly, the phase 3 placebo‐controlled trial MENDEL‐2 showed that evolocumab 140 mg Q2W used as monotherapy in 153 patients with primary hypercholesterolemia reduced LDL‐C from baseline by 57% (95% CI –59.5% to –54.6%) after 12 weeks 8. In the present study evolocumab was able to lower LDL‐C effectively in patients with mild or moderate hepatic impairment, and removal of LDL‐C through this mechanism was functional in these individuals.…”

“…Through its PCSK9‐lowering effect, administration of evolocumab increases the density of LDL‐C receptors and significantly reduces LDL‐C levels in patients with hypercholesterolemia 4, 5. In several clinical trials up to 52 weeks in duration, the safety and tolerability profile of evolocumab was similar to that of placebo 6, 7, 8, 9, 10…”

PCSK9 Inhibitors in Lipid Management of Patients With Diabetes Mellitus and High Cardiovascular Risk: A Review

“…Alirocumab and evolocumab, either alone or in combination with statins and/or other lipid‐lowering therapies, have been shown in their respective phase 3 clinical trial programs (ODYSSEY and PROFICIO [Program to Reduce LDL‐C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different Populations]) to significantly reduce LDL‐C levels by up to 60% from baseline (depending on dosing regimen; Table) in patients with hypercholesterolemia, including those with familial hypercholesterolemia, moderate to very high cardiovascular risk, and statin intolerance 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62. The inclusion/exclusion criteria and other details of each phase 3 ODYSSEY and PROFICIO trial are shown in Table S2.…”