The FDA has approved mipomersen sodium (Kynamro) injection as an addition to lipid-lowering medications and diet to treat patients with homozygous familial hypercholesterolemia (HoFH), a rare type of high cholesterol. The addition of Kynamro helps to reduce low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B, total cholesterol, and non-high density lipoprotein-cholesterol (non HDL-C), according to the agency.
HoFH, an inherited condition that affects about one out of every 1 million people in the U.S., occurs when the body is unable to remove LDL-C from the blood, causing abnormally high levels of circulating LDL-C. For those with HoFH, heart attacks and death often occur before age 30.
Kynamro (Genzyme, a Sanofi company/Isis Pharmaceuticals) is an orphan drug approval, meaning it was developed to treat a disorder affecting fewer than 200,000 people. In December 2012, the FDA approved lomitapide (Juxtapid) to reduce LDL-C, total cholesterol, apolipoprotein B, and non HDL-C in patients with HoFH.
“Kynamro, an injection given once a week, works with other lipid-lowering medications and diet to impair the creation of the lipid particles that ultimately give rise to LDL-C,” said Eric Colman, MD, deputy director of the division of metabolism and endocrinology products at the FDA’s Center for Drug Evaluation and Research.
The safety and effectiveness of Kynamro were evaluated in a clinical trial of 51 patients with HoFH. On average, levels of LDL-C fell by about 25 percent during the first 26 weeks in those receiving the drug, the FDA reported.
Kynamro carries a boxed warning on the serious risk of liver toxicity because it is associated with liver enzyme abnormalities and accumulation of fat in the liver, which could lead to progressive liver disease with chronic use. The FDA said it approved Kynamro with a Risk Evaluation and Mitigation Strategy with elements to assure safe use, including prescriber and pharmacy certification, and documentation of safe-use conditions, which requires a prescription authorization form for each new prescription. The most common adverse reactions in the clinical trial included injection site reactions, flu-like symptoms, nausea, headache and elevations in liver enzymes (serum transaminases).
The agency is requiring four postmarketing studies for Kynamro: the development of a sensitive assay that binds double-stranded (ds) DNA; a study to assess for the presence of antibodies to ds-DNA in patients treated with Kynamro; a long-term registry of patients with HoFH to determine the long-term safety of Kynamro; and an enhanced pharmacovigilance program to monitor reports of malignancy, immune-mediated reactions and hepatic abnormalities in patients treated with Kynamro.
The FDA approval also triggers a $25 million milestone payment to Isis from Genzyme.