Mipomersen in patients with homozygous familial hypercholesterolemia ( hoFH ) met its primary endpoint, with a 25 percent reduction in LDL cholesterol after 26 weeks of treatment, vs. 3 percent for placebo ( p<0.001 ).
The drug also met each of its three secondary endpoints of reduction in apolipoprotein B, total cholesterol and non-HDL cholesterol ( all p<0.001 ).

Although the patients were on maximally tolerated statins and other lipid-lowering therapies, their average LDL-C at baseline was greater than 400 mg/dL.

Consistent with previous studies evaluating Mipomersen, the most commonly observed adverse events were injection site reactions, flu-like symptoms and elevations in liver transaminases.
Of the 34 patients treated with Mipomersen, 28 completed the study. One patient discontinued due to elevations in liver transaminases.

The trial was a randomized, double-blind, placebo-controlled study that enrolled 51 homozygous familial hypercholesterolemia patients, aged 12 and older. Seven patients were aged 12 to 17.
Patients were randomized 2:1 to receive a 200 mg dose of Mipomersen or placebo via weekly injections for 26 weeks.

Familial hypercholesterolemia is a genetic disorder in which patients are unable to properly metabolize LDL cholesterol, resulting in elevated LDL-C levels.
These patients experience a markedly increased risk of premature cardiovascular disease and CVD-related death.
There are two forms of familial hypercholesterolemia: homozygous ( hoFH ), where the same defective gene is inherited from both parents, or heterozygous ( heFH ), where the defective gene is inherited from only one parent so that some function is preserved.
The homozygous form of familial hypercholesterolemia is a very rare condition estimated to affect approximately one in a million people.
HoFH patients can have LDL-C levels greater than 600 mg/dL and are at very high risk for early coronary events and sudden death. Because many patients are resistant to the lipid-lowering effects of currently available therapies, effective treatment of hoFH patients is difficult.
HeFH is a more common form of the disorder, with a prevalence of approximately one in 500, and results in untreated LDL cholesterol levels of approximately 300 mg/dL, double those of the general population.

Mipomersen is an apo-B synthesis inhibitor currently in late-stage development.

Source: Genzyme, 2009

XagenaMedicine2009


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