TY - JOUR
T1 - Pediatric experience with mipomersen as adjunctive therapy for homozygous familial hypercholesterolemia
AU - Raal, Frederick J.
AU - Braamskamp, Marjet J.
AU - Selvey, Sheryl L.
AU - Sensinger, Charlotte H.
AU - Kastelein, John J.
PY - 2016
Y1 - 2016
N2 - Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited condition resulting in severely elevated low-density lipoprotein cholesterol levels (LDL-C) leading to premature cardiovascular disease and, often, death. Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B (apo B) synthesis, lowering LDL-C levels. Mipomersen has demonstrated efficacy in adult HoFH patients, possibly providing a therapeutic option for pediatric patients. Study objectives were to summarize mipomersen efficacy and safety in the pediatric cohort of a phase 3 randomized controlled trial (RCT) and subsequent open-label extension study (OLE). Seven patients aged 12-18 years were randomized to 200-mg mipomersen or placebo weekly (26 weeks) and received mipomersen in the OLE (52 or 104 weeks). Plasma LDL-C and apo B concentrations and adverse events were assessed. All pediatric patients completed the RCT and entered OLE. The 3 mipomersen patients in the RCT experienced mean reductions from baseline to RCT end of 42.7% and 46.1% for LDL-C and apo B, respectively. Of the 4 placebo patients, 3 responded well to mipomersen during OLE, with reductions in LDL-C of 26.5%-42.1%. Three patients completed OLE treatment, and 4 patients discontinued therapy due to adverse events. Lipid level fluctuations were observed and were likely due to poor compliance. Long-term mipomersen treatment was successful regarding efficacy parameters for pediatric HoFH patients. The safety profile was consistent with other phase 3 clinical trials. Long-term compliance was an issue. Measures supporting adherence should be encouraged
AB - Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited condition resulting in severely elevated low-density lipoprotein cholesterol levels (LDL-C) leading to premature cardiovascular disease and, often, death. Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B (apo B) synthesis, lowering LDL-C levels. Mipomersen has demonstrated efficacy in adult HoFH patients, possibly providing a therapeutic option for pediatric patients. Study objectives were to summarize mipomersen efficacy and safety in the pediatric cohort of a phase 3 randomized controlled trial (RCT) and subsequent open-label extension study (OLE). Seven patients aged 12-18 years were randomized to 200-mg mipomersen or placebo weekly (26 weeks) and received mipomersen in the OLE (52 or 104 weeks). Plasma LDL-C and apo B concentrations and adverse events were assessed. All pediatric patients completed the RCT and entered OLE. The 3 mipomersen patients in the RCT experienced mean reductions from baseline to RCT end of 42.7% and 46.1% for LDL-C and apo B, respectively. Of the 4 placebo patients, 3 responded well to mipomersen during OLE, with reductions in LDL-C of 26.5%-42.1%. Three patients completed OLE treatment, and 4 patients discontinued therapy due to adverse events. Lipid level fluctuations were observed and were likely due to poor compliance. Long-term mipomersen treatment was successful regarding efficacy parameters for pediatric HoFH patients. The safety profile was consistent with other phase 3 clinical trials. Long-term compliance was an issue. Measures supporting adherence should be encouraged
U2 - https://doi.org/10.1016/j.jacl.2016.02.018
DO - https://doi.org/10.1016/j.jacl.2016.02.018
M3 - Article
C2 - 27578117
SN - 1933-2874
VL - 10
SP - 860
EP - 869
JO - Journal of clinical lipidology
JF - Journal of clinical lipidology
IS - 4
ER -