Mipomersen can cut cholesterol levels in high risk group patients, according to study data from Genzyme Corp and Isis Pharmaceuticals Inc.
Mipomersen is a first-in-class apo-B synthesis inhibitor currently in late-stage development.
The investigative drug is intended to reduce LDL-C by preventing the formation of atherogenic lipids.
It acts by decreasing the production of apo-B, which provides the structural core for all atherogenic lipids, including LDL-C, which carry cholesterol through the bloodstream.
Data showing mipomersen’s ability to reduce cholesterol levels in patients with homozygous familial hypercholesterolemia (hoFH) were published in The Lancet.
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.
“Currently available treatments do not provide adequate lipid lowering for hoFH patients, leaving them at extraordinarily high risk for cardiovascular events,” stated 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, he added.
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.
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.
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.
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.
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.
Genzyme expects to file for U.S. and E.U. approval of mipomersen and to have made progress toward filing in other major international markets, in the first half of 2011.
These two filings may also include patients with severe hypercholesterolemia. A phase 3 study of mipomersen in this patient population is fully enrolled and data are expected in mid-2010.
The companies have also completed enrollment in a phase 3 trial involving patients at high risk for coronary heart disease, and data are anticipated in mid-2010.
Genzyme and Isis last month reported that a phase 3 study of mipomersen in heterozygous familial hypercholesterolemia (heFH) met its primary endpoint with a 28 percent reduction in LDL-cholesterol after 26 weeks of treatment, compared with an increase of 5 percent for placebo. The trial also met each of its secondary endpoints. Data will be submitted for presentation at a future medical meeting.
Genzyme is a leading biotechnology company. Genzyme’s products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune disease, and diagnostic testing.
Isis is a company exploring RNA-based therapies. The Company has successfully commercialized the world’s first antisense drug and has 22 drugs in development. Isis’ drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer.
Isis’ partners are developing antisense drugs invented by Isis to treat a wide variety of diseases.
Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics.
Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,600 issued patents worldwide.