FDA approves mipomersen sodium for HoFH

FDA has approved mipomersen sodium (Kynamro, Genzyme and Isis Pharmaceuticals) once-a-week injection as an addition to lipid-lowering medications and diet to treat patients with a rare type of high cholesterol called homozygous familial hypercholesterolemia (HoFH). 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).

“The release of new orphan drugs should always be viewed as a movement in the right direction because brings attention to populations that are not typically targeted when it comes to drug developments,” said Formulary Advisor Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center, in Webster, Texas. “The approval of the lipid-lowering medication, Kynamro, to be used in conjunction with other lipid lowering medications in individuals with homozygous familiar hypercholesterolemia serves as another landmark drug approval to treat individuals who have rare conditions but unfortunately can have limited therapeutic options on the market when it comes to the treatment of their conditions.”

HoFH, an inherited condition that affects about 1 out of every 1 million people in the United States, occurs when the body is unable to remove LDL-C, often called “bad” cholesterol, from the blood causing abnormally high levels of circulating LDL-C. For those with HoFH, heart attacks and death often occur before aged 30 years.

In December 2012, FDA approved lomitapide (Juxtapid, Aegerion Pharmaceuticals) to reduce LDL-C, total cholesterol, apolipoprotein B, and non HDL-C in patients with HoFH.

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% during the first 26 weeks in those receiving the drug. 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.

FDA approved Kynamro with a Risk Evaluation and Mitigation Strategy (REMS) 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).

FDA 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.