FDA approves Juxtapid for rare cholesterol disease

The FDA has approved lomitapide (Juxtapid, Aegerion Pharmaceuticals) to reduce cholesterol in patients with homozygous familial hypercholesterolemia, but the drug's labeling included a boxed warning citing the risk of liver toxicity.

Lomitapide is intended for use in combination with a low fat diet and other lipid-lowering treatments for patients with homozygous familial hypercholesterolemia, a rare inherited condition that makes the body unable to remove low-density lipoprotein (LDL) cholesterol from the blood. These patients are at high risk of developing atherosclerosis. For those with the disease, MIs and death often occur before age 30.

The drug reduces LDL cholesterol, total cholesterol, apolipoprotein B and non-high-density lipoprotein cholesterol by impairing the creation of the lipid particles that ultimately give rise to LDL. But it also reduces the absorption of fat-soluble nutrients and interacts with several other medications. Consequently, patients should take supplements that contain fat-soluble vitamins and essential fatty acids daily while taking lomitapide.

Juxtapid carries a boxed warning regarding a serious risk of liver toxicity because it is associated with liver enzyme abnormalities and accumulation of fat in the liver, which could potentially lead to progressive liver disease with chronic use.

Its safety and effectiveness were evaluated in a clinical trial of 29 patients with homozygous familial hypercholesterolemia. On average, levels of LDL cholesterol fell by approximately one-half during the first 26 weeks among those who tolerated the drug. The effect of Juxtapid on cardiovascular morbidity and mortality has not been determined.

Because of the risk of liver toxicity, the FDA approved Juxtapid with a Risk Evaluation and Mitigation Strategy that consists of elements to ensure safe use including documentation of safe-use conditions consisting of a prescription authorization form that will be required to accompany each new prescription. Cambridge, Mass.-based Aegerion said in a release that it will certify all healthcare providers who prescribe Juxtapid and the pharmacies that will dispense it.

The FDA is requiring three postmarketing studies for Juxtapid: an animal study to evaluate the potential for toxicity in children and teens; a long-term registry of patients with homozygous familial hypercholesterolemia treated with Juxtapid to determine the long-term safety; and an enhanced pharmacovigilance program to monitor reports of malignancy, teratogenicity, and hepatic abnormalities.

The most common adverse reactions in the clinical trial included diarrhea, nausea, vomiting, indigestion and abdominal pain.