Date: 2011-06-28
Type of information: Results
phase: 3
Announcement: results
Company: Genzyme (USA - MA), a Sanofi company (France)
Product: mipomersen
Action
mechanism: Mipomersen is a first-in-class apo-B synthesis inhibitor and acts by blocking the production of apolipoprotein B (apoB), the protein that provides the structural core for these atherogenic particles, including LDL and lipoprotein-a (Lp(a)).
Disease: heterozygous familial hypercholesterolemia
Therapeutic area: Cardiovascular diseases - Genetic diseases - Rare diseases
Country:
Trial details:
Latest
news: Genzyme, a Sanofi company, and Isis Pharmaceuticals Inc announced that two additional analyses from phase 3 studies of mipomersen were presented at the 79th European Atherosclerosis Society (EAS) Congress. In a presentation entitled “Mipomersen, A First-in-Class ApoB Synthesis Inhibitor, Lowers Lp(a) in Patients with Heterozygous Familial Hypercholesterolemia (HeFH) and High Baseline Lp(a): Results from two Phase 3 studies,” Elisabeth Steinhagen-Thiessen, M.D., of the Lipid Ambulatory Clinic, University of Berlin, Germany, focused on the effects of mipomersen on elevated Lp(a) levels.
Data from two randomized, placebo-controlled phase 3 trials in patients with HeFH showed that mipomersen reduced Lp(a), LDL-C, and other measures of atherogenic lipoproteins when added to existing lipid-lowering therapy. One study included 124 HeFH patients with CAD, and the other included 58 severe HeFH patients. All of the patients were already taking a maximally tolerated dose of a statin, as well as additional lipid-lowering drugs in most cases. Both trials met all of their primary, secondary and tertiary endpoints. In these trials, mipomersen decreased LDL-C by 28 and 36 percent compared with increases of 5 and 13 percent for placebo, respectively (both p<0.001), meeting primary endpoints in both studies.
In addition to evaluating percent reduction in LDL-C as their primary endpoints, both trials also evaluated percent reduction in Lp(a) as tertiary endpoints. Most patients in the two trials (71 and 62 percent) had elevated Lp(a) levels >20 mg/dl at baseline. Mipomersen decreased Lp(a) by a median 21 and 39 percent, compared with zero and five percent for the placebo groups (both p<0.001). Mipomersen lowered Lp(a) by ? 50 percent in 22 percent of mipomersen patients across both studies. The reductions observed were in addition to those achieved with the patients’ existing therapeutic regimens.
In a presentation entitled “Mipomersen, an ApoB Synthesis Inhibitor, Might Reduce Necessity for Lipid Apheresis in CAD,” K.G. Parhofer, M.D., of Ludwig-Maximilians University, Munich, Germany, focused on mipomersen’s potential to reduce the necessity for lipid-apheresis by lowering LDL-C values below thresholds for apheresis eligibility. Patients with severe forms of FH may be eligible for this treatment, a dialysis-like procedure where blood is filtered through a machine to remove excess cholesterol. Country-specific LDL-C thresholds to determine eligibility for apheresis can range from ? 100 mg/dL to ? 160 mg/dL. However, many eligible patients are not on apheresis because of lack of availability, high cost and negative impact on quality of life. In the phase 3 trial in HeFH patients with CAD, an additional analysis revealed that mipomersen reduced the percentage of patients with LDL-C levels ? 160 mg/dL by 95 percent (from 39 percent to 2 percent); with LDL-C levels ? 130 mg/dL by 74 percent (from 62 percent to 16 percent); and with LDL-C levels ? 100 mg/dL by 45 percent (from 98 percent to 54 percent). The reductions observed were in addition to those achieved with the patients’ existing therapeutic regimens. No significant changes in LDL-C were observed in placebo-treated patients.
Genzyme expects to file for EU marketing approval of mipomersen for the treatment of patients with homozygous (Ho) FH and severe HeFH early in the third quarter of this year. Genzyme also expects to file for U.S. approval for the HoFH indication in the second half of this year.
