Isis Pharmaceuticals Inc. (ISIS) announced the publication of new data in the journal Circulation Research demonstrating that antisense targeting of apolipoprotein C-III or apoC-III resulted in significant reductions in apoC-III and triglycerides, each an independent risk factor for cardiovascular disease.
Hypertriglyceridemia is a serious medical condition associated with premature coronary artery disease and an increased risk for pancreatitis.
Isis is developing its antisense apoC-III inhibitor, ISIS-APOCIIIRx, for the treatment of patients with severe hypertriglyceridemia and plans to report top-line data in the middle of this year.
In the published data, treatment with an antisense compound targeting apoC-III produced a variety of potential cardio-protective effects including significant dose-dependent reductions of apoC-III and triglycerides in all models and species, including man. In addition, treatment with an antisense compound targeting apoC-III resulted in enhanced triglyceride clearance from blood following a high-fat meal, reduction of VLDL particles and a slight increase in HDL-C levels. In all models and in the Phase 1 study, antisense inhibition of apoC-III was well tolerated.
The company stated that the data were consistent across multiple preclinical models and species and in a Phase 1 study in healthy volunteers demonstrating that Isis' antisense technology was able to produce predictable and consistent responses among different animal models that translate into corresponding activity in man.
In the Phase 1 study, treatment with ISIS-APOCIIIRx was well tolerated and produced rapid, dose-dependent median reductions of up to 44 percent in plasma triglycerides and up to 78 percent in apoC-III protein, with two out of the three subjects in the highest dose group achieving undetectable levels of apoC-III.
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