Abstract 11321: Evaluation of Cardiovascular Events With the Administration of Mipomersen an Antisense Apo B100 Synthesis Inhibitor: Results From the Phase 3 Program
Objective: In January 2013, mipomersen was approved in the US to treat homozygous familial hypercholesterolemia. This study retrospectively evaluated the cardiovascular (CV) event rates in patients participating in phase 3 randomized controlled trials (RCT) of mipomersen vs placebo. The clinical trials included patients with and without familial hypercholesterolemia (FH).
Methods: Retrospective analyses using datasets from phase 3 clinical trials in 4 different populations including homozygous (HoFH) were conducted to determine if any differences existed between mipomersen-treated patients compared with placebo-treated patients for major adverse cardiac events (MACE). Relative risk of CV events was analyzed and estimated by the FDA based on results of a broad and narrow search of CV events and measure of seriousness using pre-defined search terms.
Results: A total of 129 placebo subjects and 261 mipomersen subjects were in the four phase 3 clinical studies (NCT00607373, NCT00706849, NCT00794664, NCT00770146). The most common SAEs were cardiac disorders; HoFH population: placebo, 0 (0.0%) vs. mipomersen, 1 (2.9%); all Phase 3: placebo, 4 (3.1%) vs. mipomersen, 10 (3.8%). The MACE incidence amongst the pooled Phase 3 dataset was similar in the mipomersen-treated group (3.4%) compared with the placebo-treated group (3.1%). The estimated relative risk and 95% CI for the broad and narrow CV search was 1.10 (0.52, 2.35) and 0.64 (0.24, 1.68), respectively. Overall, there was no statistically significant evidence of a difference in relative risk for CV events between mipomersen and placebo in either of these searches. An independent analysis using retrospective adjudication performed by SOCAR research, showed no difference in the incidence of MACE events per 100 patient-years in mipomersen-treated (5.4) versus placebo-treated (5.4) patients in the pooled Phase 3 study population.
Conclusion: The phase 3 clinical program was not powered to evaluate the impact of mipomersen on CV events. It is nonetheless reassuring to find no difference in the CV event rate between the placebo and mipomersen groups in this program. The CV event profile (including MACE events) of mipomersen will continue to be monitored in a prospective, placebo-controlled trial.
- © 2013 by American Heart Association, Inc.