The objective of a study was to evaluate the efficacy and safety of extended dosing with Mipomersen ( Kynamro ) in patients with familial hypercholesterolaemia taking maximally tolerated lipid-lowering therapy.
A planned interim analysis of an ongoing, open-label extension trial in patients ( n = 141 ) with familial hypercholesterolaemia receiving a subcutaneous injection of 200 mg Mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks, was performed.
The mean changes in low-density lipoprotein cholesterol ( LDL-C ) from baseline to weeks 26 ( n = 130 ), 52 ( n = 111 ), 76 ( n = 66 ), and 104 ( n = 53 ) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively.
Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL cholesterol and apolipoprotein B levels.
Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively.
The long-term safety profile of Mipomersen was similar to that reported in the associated randomized placebo-controlled phase 3 trials.
Adverse events included injection site reactions and flu-like symptoms.
There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued Mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation.
The median alanine aminotransferase ( ALT ) level showed a similar trend over time.
In conclusion, long-term treatment with Mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. ( Xagena )
Santos RD et al, Eur Heart J 2015;36: 566-575