Date: 2011-04-05
Type of information: Results
phase: 3
Announcement: results
Company: Genzyme (USA - MA), a Sanofi company (France)
Product: mipomersen
Action
mechanism: apo-B synthesis inhibitor
Disease: high cholesterol at high risk for CHD
Therapeutic area: Cardiovascular diseases
Country:
Trial
details: The first study was a double-blind, placebo-controlled trial included 158 patients with hypercholesterolemia (LDL-C ≥ 100 mg/dL) and at high risk of developing CHD who were taking a maximally tolerated dose of a statin. Patients were randomized 2:1 to receive a self-administered 200 mg subcutaneous injection of mipomersen or placebo weekly for 26 weeks.
Latest
news: Genzyme announced that data from two phase 3 studies of mipomersen in patients who had high cholesterol levels while on lipid-lowering therapy were presented at the American College of Cardiology’s 60th Annual Scientific Session. Results of a phase 3 study of mipomersen in patients with high cholesterol at high risk for CHD were also presented in a poster at ACC.
In the first study, mipomersen reduced LDL-C, the primary endpoint, by 37 percent compared with a 5 percent reduction for placebo (p<0.001). The study, which was presented by William Cromwell, M.D., of the Presbyterian Cardiovascular Institute, Charlotte, N.C., also met each of its secondary endpoints.
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. Patients treated with mipomersen also experienced statistically significant reductions in apo-B, Lp(a), non-HDL-cholesterol and total cholesterol. Study results are based on an intent-to-treat analysis (full analysis set).
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. The most common adverse events were injection site reactions and flu-like symptoms. There was one death during the on-treatment study period due to acute myocardial infarction in a patient treated with placebo. During the post-treatment follow-up period, one patient died due to liver failure, acetaminophen toxicity, pneumonia and myocardial infarction 149 days after receiving the last dose of mipomersen treatment.
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. As measured by MRI, mipomersen-treated patients had a moderate increase in liver fat from baseline compared with placebo-treated patients. In general, increases in liver transaminases and liver fat appeared to be associated with the greatest reductions of LDL-C, and in the six-month follow-up period after treatment was discontinued, returned toward baseline along with all lipids, including LDL-C, apo-B and Lp(a).
