AI Article Synopsis
- Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder that significantly raises LDL cholesterol levels, leading to serious heart problems. Mipomersen, a drug that reduces LDL-C by targeting apolipoprotein B, has shown promise for treating this condition.
- In a study involving seven patients aged 12-18, those treated with mipomersen experienced notable reductions in LDL-C and apo B levels compared to those on placebo, with some patients transitioning to mipomersen from placebo showing improvements during the open-label extension phase.
- Despite the effectiveness of mipomersen in lowering cholesterol, issues with long-term treatment adherence were reported, highlighting the need for strategies to improve patient compliance.
Article Abstract
Background: 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).
Methods: 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.
Results: 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.
Conclusions: 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.
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| http://dx.doi.org/10.1016/j.jacl.2016.02.018 | DOI Listing |
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