BETHESDA, MD 26 December 2012—FDA and Aegerion Pharmaceuticals Inc. recently announced the approval of lomitapide, or Juxtapid, as part of the overall treatment for patients who are homozygous for familial hypercholesterolemia, a disorder that affects about 1 in 1 million people.
Patients who are homozygous for the inherited disorder typically have a low-density-lipoprotein (LDL) cholesterol concentration of at least 400 mg/dL without treatment, according to the company.
A typical long-term consequence for patients, FDA said, is myocardial infarction and death before age 30.
Lomitapide, the company said, inhibits microsomal triglyceride transfer protein, which reduces the production of very-low-density-lipoprotein cholesterol, the precursor of LDL cholesterol.
Twenty-six weeks of lomitapide therapy in addition to other lipid-lowering treatments lowered the LDL cholesterol concentration by an average of 40% in the 29 adult patients who participated in the company's multinational study, according to the drug's labeling (PDF). Their mean LDL cholesterol concentration dropped from 336 mg/dL down to 190 mg/dL.
All but 2 of the patients, the labeling states, had adverse gastrointestinal reactions to lomitapide therapy.
Ten patients, the labeling also states, had at least one elevation in aspartate transaminase (AST) or alanine transaminase (ALT) concentration exceeding three times the upper limit of the normal range during the 78-week study. Hepatic fat content increased by up to 18%.
Patients' risk for hepatotoxicity during lomitapide therapy is the subject of the labeling's boxed warning and the reason, the company said, for the risk evaluation and mitigation strategy and certification program for prescribers and pharmacies.
There is also a medication guide that explains to patients the risk of hepatotoxicity during therapy and the potential of the drug to harm unborn babies.
Lomitapide must not be taken by patients who are pregnant. The drug is also contraindicated in patients with moderate or severe hepatic impairment, active liver disease, or unexplained persistent abnormal liver function test results. Another contraindication is concomitant use with moderate or strong inhibitors of cytochrome P-450 isoenzyme 3A4.
The labeling recommends a starting dosage of 5 mg once daily, with gradual increases up to a maximum of 60 mg once daily. All doses are to be taken with water, without food, and at least two hours after the evening meal. The product will be available in 5-, 10-, and 20-mg capsules.
Lomitapide's inhibition of microsomal triglyceride transfer protein decreases the synthesis of chylomicrons and thus the absorption of fat-soluble vitamins and fatty acids from the small intestine. The labeling recommends patients take daily supplements of vitamin E, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid.
During a conference call with investment analysts on December 24, Aegerion's chief executive officer said the company plans to launch Juxtapid in January and certify only specialty pharmacies to dispense the drug.