Patients treated with mipomersen had an average LDL-C at baseline of 123 mg/dL. At the end of the study, these patients had an average LDL-C level of 75 mg/dL, representing an average LDL-C reduction of 48 mg/dL (37 percent). Half of the mipomersen-treated patients achieved LDL-C levels of less than 70 mg/dL, a recognized treatment goal for high-risk patients. The reductions observed in the study were in addition to those achieved with the patients' existing maximally tolerated statin regimens. The trial also met each of its three secondary endpoints with statistically significant reductions in apo-B, non-HDL-cholesterol and total cholesterol. Study results are based on an intent-to-treat analysis (full analysis set). Detailed results will be submitted for presentation at a medical meeting.

Of the 105 patients treated with mipomersen, 60 completed treatment; of the 53 patients treated with placebo, 44 completed treatment. Twenty-six of the discontinuations in the mipomersen group were reported as being related to adverse events, the nature of which was generally similar to previous studies. Two of the discontinuations in the placebo group were reported as being related to adverse events. There was one death in the study due to acute myocardial infarction in a patient treated with placebo.

Elevations in ALTs in patients treated with mipomersen were observed that were generally similar in character with those seen in other studies. In this study, 10 percent of patients had persistent ALT elevations above 3X ULN during the treatment period. Persistent is defined as consecutive elevations at least one week apart. In many cases, these elevations were associated with increased hepatic fat content, as measured by MRI. No patients had changes in laboratory tests indicative of clinically significant hepatic dysfunction, and there were no Hy's Law cases.

"The completion of these phase 3 studies is a significant milestone for the mipomersen program, for antisense technology and for patients in need," said Isis Pharmaceuticals Chairman and CEO Stanley T. Crooke. "Mipomersen's lipid-lowering activity demonstrates the value antisense drugs can bring to patients. Our robust pipeline is evidence of the efficiency of our technology and the potential value we can create."

Late-Stage Development Plan

Genzyme's initial U.S. and E.U. regulatory filings for mipomersen will seek marketing approval for the treatment of patients with the genetic disease homozygous FH (hoFH). These initial filings may also include patients with severe hypercholesterolemia. In the first half of 2011, Genzyme expects to submit the initial U.S. and E.U. filings, and to have made progress toward filing in other major international markets.

As previously reported, the phase 3 study of mipomersen in hoFH patients met its primary endpoint with 25 percent LDL-C reduction, and results were presented at last year's American Heart Association meeting. Genzyme and Isis in February reported that the phase 3 study of mipomersen in heFH met its primary endpoint with a 28 percent LDL-C reduction, and data will be presented at the European Society of Cardiology meeting this month. In addition, studies are ongoing and planned to evaluate alternative dosing regimens.

SOURCE Genzyme Corp. and Isis Pharmaceuticals Inc.