TY - JOUR
T1 - Effect of Mipomersen, an Apolipoprotein B Synthesis Inhibitor, on Low-Density Lipoprotein Cholesterol in Patients With Familial Hypercholesterolemia
AU - Akdim, Fatima
AU - Visser, Maartje E.
AU - Tribble, Diane L.
AU - Baker, Brenda F.
AU - Stroes, Erik S. G.
AU - Yu, Rosie
AU - Flaim, Joann D.
AU - Su, John
AU - Stein, Evan A.
AU - Kastelein, John J. P.
PY - 2010
Y1 - 2010
N2 - A randomized, double-blind, placebo-controlled, dose-escalation study was conducted to examine the,efficacy and safety of mipomersen (ISIS 301012), an antisense inhibitor of apolipoprotein B, when added to conventional lipid-lowering therapy for patients with heterozygous familial hypercholesterolemia. A total of 44 patients were enrolled and were separated into 4 cohorts, with doses ranging from 50 to 300 mg (4:1 active treatment/placebo ratio). Patients received 8 doses subcutaneously during a 6-week treatment period. Patients assigned to the 300-mg dose continued for an additional 7 weeks with once-per-week dosing. The primary efficacy end point was the percentage of change from baseline to week 7 in low-density lipoprotein (LDL) cholesterol. Safety was assessed using the laboratory test results and according to the incidence, severity, and relation of adverse events to drug dose. Mipomersen produced significant reductions in LDL cholesterol and other atherogenic apolipoprotein B-containing lipoproteins. After 6 weeks of treatment, the LDL cholesterol level was reduced by 21% from baseline in the 200-mg/week dose group (p <0.05) and 34% from baseline in the 300-mg/week dose group (p <0.01), with a concomitant reduction in apolipoprotein B of 23% (p <0.05) and 33% (p <0.01), respectively. Injection site reactions were the most common adverse event. Elevations in liver transaminase levels times the upper limit of normal) occurred in 4 (11%) of 36 patients assigned to active treatment; 3 of these patients were in the highest dose group. In conclusion, mipomersen has an incremental LDL cholesterol lowering effect when added to conventional lipid-lowering therapy. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1413-1419)
AB - A randomized, double-blind, placebo-controlled, dose-escalation study was conducted to examine the,efficacy and safety of mipomersen (ISIS 301012), an antisense inhibitor of apolipoprotein B, when added to conventional lipid-lowering therapy for patients with heterozygous familial hypercholesterolemia. A total of 44 patients were enrolled and were separated into 4 cohorts, with doses ranging from 50 to 300 mg (4:1 active treatment/placebo ratio). Patients received 8 doses subcutaneously during a 6-week treatment period. Patients assigned to the 300-mg dose continued for an additional 7 weeks with once-per-week dosing. The primary efficacy end point was the percentage of change from baseline to week 7 in low-density lipoprotein (LDL) cholesterol. Safety was assessed using the laboratory test results and according to the incidence, severity, and relation of adverse events to drug dose. Mipomersen produced significant reductions in LDL cholesterol and other atherogenic apolipoprotein B-containing lipoproteins. After 6 weeks of treatment, the LDL cholesterol level was reduced by 21% from baseline in the 200-mg/week dose group (p <0.05) and 34% from baseline in the 300-mg/week dose group (p <0.01), with a concomitant reduction in apolipoprotein B of 23% (p <0.05) and 33% (p <0.01), respectively. Injection site reactions were the most common adverse event. Elevations in liver transaminase levels times the upper limit of normal) occurred in 4 (11%) of 36 patients assigned to active treatment; 3 of these patients were in the highest dose group. In conclusion, mipomersen has an incremental LDL cholesterol lowering effect when added to conventional lipid-lowering therapy. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1413-1419)
U2 - https://doi.org/10.1016/j.amjcard.2010.01.003
DO - https://doi.org/10.1016/j.amjcard.2010.01.003
M3 - Article
C2 - 20451687
SN - 0002-9149
VL - 105
SP - 1413
EP - 1419
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 10
ER -