Genzyme, Isis Pharmaceuticals: Phase 3 study of mipomersen in hoFH patients meets primary endpoint

Genzyme Corp. (NASDAQ: GENZ) and Isis Pharmaceuticals Inc. (NASDAQ: ISIS) today announced that data from a phase 3 study of mipomersen in patients with homozygous familial hypercholesterolemia (hoFH) were published in The Lancet. This study met its primary endpoint, resulting in an average LDL-C reduction of greater than 100 mg/dL in this very high-risk patient population.

“Mipomersen has the potential to set a new standard of care for this difficult-to-treat disease.”

“Currently available treatments do not provide adequate lipid lowering for hoFH patients, leaving them at extraordinarily high risk for cardiovascular events,” said Professor Frederick J. Raal, M.D., Ph.D., Director of the Carbohydrate and Lipid Metabolism Research Unit at the University of the Witwatersrand in South Africa, and the study’s primary investigator. “Mipomersen has the potential to set a new standard of care for this difficult-to-treat disease.”

The trial, one of the largest conducted to date in this rare patient population, was designed to test the efficacy and safety of adding mipomersen to substantial lipid-lowering therapy. Patients treated with mipomersen had a 25 percent LDL-C reduction in an intent-to-treat analysis. In addition to meeting its primary endpoint, the trial also met each of its secondary and tertiary endpoints, which included statistically significant reductions in apolipoprotein-B, total cholesterol, non-HDL cholesterol, Lp(a), VLDL-C and triglycerides.

Familial hypercholesterolemia (FH) is a genetic disorder that results in elevated LDL cholesterol levels. FH patients experience a markedly increased risk of premature cardiovascular disease (CVD) and CVD-related death. There are two forms of FH: homozygous, estimated to affect approximately one in a million people worldwide; and heterozygous, a more common form of the disorder with a prevalence of approximately one in 500. In patients with hoFH, the first cardiovascular events can occur in childhood or adolescence. Without lipid-lowering therapy, hoFH patients rarely live beyond age 30.

Although all but one of the 51 patients in the phase 3 study were being treated with lipid-lowering therapy, their average LDL-C at baseline was greater than 400 mg/dL. The LDL-C reductions observed in the study were in addition to those achieved with the patients’ existing therapeutic regimens.

“These results are exciting news for hoFH patients, who are in great need of new treatment options,” said Mary McGowan, M.D., of the Concord Hospital Cholesterol Treatment Center, Concord, NH, and a board member of the National Lipid Association. “Mipomersen could make a major difference for these patients.”

The trial was a randomized, double-blind, placebo-controlled study that enrolled hoFH patients aged 12 and older; seven patients were aged 12 to 17. Patients were randomized 2:1 to receive a 200 mg dose of mipomersen or placebo via weekly subcutaneous injections for 26 weeks. The study was conducted at 10 sites in seven countries in North America, Europe, Asia, South America and Africa.

Consistent with previous studies evaluating mipomersen, among the most commonly observed adverse events were injection site reactions, flu-like symptoms and elevations in liver transaminases. Of the 34 patients treated with mipomersen, 28 completed the study. One patient discontinued due to elevations in liver transaminases.

Results of this study were presented by Professor Raal at the annual American Heart Association meeting in November 2009. Study investigator Dr. William Cromwell, Chief of the Division of Atherosclerosis and Lipoprotein Disorders at the Presbyterian Cardiovascular Institute in Charlotte, North Carolina, also presented at AHA on the effects of mipomersen on Lp(a) within the trial.