The Endocrinologic and Metabolic Drugs Advisory Committee of the US Food and Drug Administration (FDA) has voted 9 to 6 that Genzyme had provided sufficient efficacy and safety data to support the marketing of Kynamro (mipomersen sodium) for the treatment of patients with Homozygous Familial Hypercholesterolemia (HoFH).
Many people with HoFH have aggressive cardiovascular disease beginning in childhood, and even with today’s therapies remain at significant risk of cardiovascular events.
"We are very encouraged by the support for Kynamro at today’s advisory committee meeting, which marks a significant and positive step in our efforts to bring this important new therapy to patients and families affected by this often unrecognized genetic disorder,” said David Meeker, president and CEO, Genzyme. “There is still a great need for the HoFH patients, who have exhausted conventional medications and still have LDL cholesterol levels 2-4 times above normal. Genzyme looks forward to working with the FDA as it completes its review of the Kynamro application.”
The Committee's input will be considered by the FDA in its review of the New Drug Application for Kynamro. The FDA is not bound by the Committee's guidance, but takes its advice into consideration when reviewing investigational medicines. Genzyme submitted the NDA on March 29, 2012, and the FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of January 29, 2013. An application for marketing approval of Kynamro is also pending in the European Union.
In considering the benefits and risks associated with Kynamro, the Committee reviewed data from one pivotal phase III double-blind, placebo controlled study in HoFH patients, three supportive phase III studies in other high-risk hypercholesterolemia populations and an ongoing long term extension study.
“ Kynamro could represent a significant advance for patients with HoFH, who are unable to adequately control their LDL-C and remain at significant risk of a cardiac event. We are pleased with the positive recommendations from the advisory committee and look forward to the FDA’s decision early next year,” said B. Lynne Parshall, chief operating officer and CFO of Isis. “Kynamro is an example of our leadership in the field of RNA-targeted therapies and provides compelling evidence of the power of our drug discovery technology to create potent and specific drugs that could play an important role in the treatment of disease.”
Kynamro is the registered trade name submitted to health authorities for the investigational agent mipomersen sodium. Its is a first-in-class apo-B synthesis inhibitor currently under regulatory review for patients with homozygous familial hypercholesterolemia (HoFH) to further reduce LDL cholesterol (LDL-C) in patients already maintaining a stable regimen of maximally tolerated lipid lowering therapies, and who require additional, significant lipid lowering therapy. It is intended to reduce LDL-C by preventing the formation of atherogenic lipoproteins, the particles that carry cholesterol through the bloodstream. Kynamro acts by blocking the production of, apolipoprotein B (apo B), the protein that provides the structural core for these atherogenic particles, including LDL and lipoprotein-a (Lp(a)).
FH is a genetic disease that results in elevated LDL-C levels and family patterns of increased risk of premature heart disease and heart disease-related death. FH patients have inherited abnormalities in liver cells that are responsible for clearing LDL particles from the blood. FH is autosomal dominant, which means that all first-degree relatives of FH patients have a 50 percent chance of having the disease as well, making early detection through family screening critically important.
The most severe FH patients have LDL-C levels that are two to four times higher than recommended levels, even when taking multiple cholesterol-lowering medications. These people, who are characterized as having severe FH, include: those who have inherited the disease from both parents (HoFH) and those who have inherited it from only one parent, and have a particularly severe form of the disease (Severe HeFH) defined as those people who are maximally treated and still have LDL-C greater than 200 mg/dL (5.1 mmol) with coronary heart disease or greater than 300 mg/dL (7.1 mmol) without coronary heart disease. People with HoFH may have aggressive heart disease beginning in childhood, and even with today’s therapies remain at significant risk of cardiovascular events.
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