NDA Submission and Phase 3 Trial Update for Kynamro for Homozygous Familial Hypercholesterolemia

Genzyme and Isis Pharmaceuticals announced that Genzyme has submitted a New Drug Application (NDA) to the FDA seeking approval for Kynamro (mipomersen sodium) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH).

The FDA submission for Kynamro is supported by the largest clinical trial conducted to date in the HoFH patient population. In the randomized, double-blind, placebo controlled, multi-center trial, significant reductions were observed in all atherogenic lipoproteins evaluated (including LDL-C, Apo B and Lp(a)) for patients receiving Kynamro who are already receiving a regimen of maximally tolerated lipid-lowering therapies including statins.

This morning, the companies announced new two-year data from a phase 3 long-term extension study of Kynamro in patients with familial hypercholesterolemia (FH). Patients treated with Kynamro for two years maintained robust reductions in LDL-C and all other Apo B containing atherogenic lipoproteins measured.

Data presented included 141 patients who had previously completed one of the three phase 3 studies: homozygous FH, severe hypercholesterolemia, or the heterozygous FH. These studies were six months long and required patients to be on stable maximally tolerated lipid-lowering therapy throughout the study. To date, 63 patients remain on or have completed treatment with 40 patients consenting to participate for another two years of treatment - a total of four years of treatment.

In this study, sustained reductions in LDL-C with a mean reduction of 28% in LDL-C at six months and at two years were observed in patients treated with Kynamro. Changes in liver fat were observed in some patients where the overall median change stabilized and then declined with continued treatment. The median change from baseline in percent liver fat increased from 5% at 26 weeks, to 13% at 52 weeks, and returned to 5% at 104 weeks. Results represent those patients in the extension study at each assessment period: 60 patients at 26 weeks, 31 patients at 52 weeks, and 39 patients at 104 weeks. The median change reflects both patients who continued at full dose as well as those with dose adjustments and dose interruptions. Upon treatment discontinuation, changes in liver fat returned towards normal.

Kynamro is a first-in-class apo-B synthesis inhibitor that reduces LDL-C by preventing the formation of atherogenic lipids. It acts by decreasing the production of apo-B, which provides the structural core for all atherogenic lipids, including LDL-C, which carry cholesterol through the bloodstream.

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