The FDA has approved the lipid-lowering drug lomitapide (Juxtapid) as add-on therapy in patients with a rare lipid disorder, the agency announced Wednesday.
The drug is for homozygous familial hypercholesterolemia (HoFH) patients and is designed to reduce low-density lipoprotein (LDL) cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol.
The drug should be paired with a low-fat diet and other lipid-lowering medications, the agency stated.
HoFH is a rare genetic condition that, if untreated, can cause extremely High cholesterol levels, typically between 400 mg/dL and 1,000 mg/dL. HoFH affects roughly one in 1 million people in the U.S.
The once-daily capsule inhibits a particular protein which reduces the cholesterol that the liver and intestines assemble and secrete into the bloodstream. While statins are the standard method for treating High cholesterol, people with HoFH lack LDL receptors, a deficiency which lowers statins’ efficacy.
Lomitapide’s safety and efficacy was demonstrated in a single-arm, open-label study of 29 HoFH patients that showed a 40% reduction in LDL cholesterol on average after 26 weeks when paired with other lipid-lowering drugs. The baseline average dropped from 336 mg/dL to 190 mg/dL in the study.
However, 10% of the 29 patients in the 26-week study had at least one serious adverse event, including liver toxicity. That percentage rose to 22% during the first 120 days of an extension trial.
Ten of the 29 studied patients had liver enzymes alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at least three times greater than normal, the FDA said.
As a result, the drug carries a boxed warning for a serious risk of liver toxicity because of its link to liver enzyme abnormalities and accumulation of fat in the liver, potentially leading to progressive liver disease with chronic use.
However, there were no clinically meaningful elevations of total bilirubin, international normalized ratio, or alkaline phosphatase with the drug, all of which are additional markers of harmful liver effects.
Other adverse events included diarrhea, vomiting, indigestion, and abdominal pain.
Manufacturer Aegerion Pharmaceuticals of Cambridge, Mass., is required to perform three postmarketing studies for lomitapide, including a long-term registry of patients to track the drug’s safety over time.
Members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-2 to recommend approval for the new drug at an October meeting.
“Juxtapid, in addition to diet changes and other cholesterol-lowering treatments, is a new option for those suffering with HoFH and the serious health consequences resulting from this condition,” said Eric Colman, MD, deputy director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research in a statement.
As stated at the time of the advisory committee meeting, the FDA has required a risk evaluation and mitigation strategy (REMS) that includes a program requiring all prescribers and pharmacies to achieve special certification. Patients will need an authorization form to accompany each new prescription.
The drug has not been proven in non-HoFH patients or children.
Lipid disorders (Cholesterol)
Lipid disorders are the broad term for abnormalities of cholesterol and triglycerides. Lipid abnormalities are associated with an increased risk for vascular disease, and especially heart attacks and strokes. Abnormalities in lipid disorders are a combination of genetic predisposition as well as the nature of dietary intake. Many lipid disorders are associated with being overweight. Lipid disorders may also be associated with other diseases including diabetes, the metabolic syndrome (sometimes called the insulin resistance syndrome), underactive thyroid or the result of certain medications (such as those used for anti-rejection regimens in people who have had transplants).
There is accumulating evidence that management of cholesterol and triglyceride disorders is associated with the reduced risk for heart attacks and strokes. This is especially true in patients seen by endocrinologists who have diabetes mellitus or other problems associated with obesity.
Bristol-Myers Squibb originally developed lomitapide for High cholesterol, but halted development when a trial saw a high patient dropout rate because of gastrointestinal side effects.
The known risk factors for High cholesterol that you cannot control include:
Gender - Before menopause, women usually have lower total cholesterol levels than men of the same age. As women and men age, their blood cholesterol levels rise until the age of about 60 to 65 years.
Age - Your risk increases if you are a man aged 45 years or older or a woman aged 55 years or older.
Heredity - Your genes influence how high your LDL (bad) cholesterol is by affecting how fast LDL is made and removed from the blood. One specific form of inherited High cholesterol that affects 1 in 500 people, called familial hypercholesterolemia, leads to early heart disease. Even if you do not have a specific genetic form of High cholesterol, genes play a role in influencing your LDL cholesterol level.
The factors for High cholesterol that you can control include:
Diet - The saturated fat and cholesterol in the food you eat raise total and LDL-cholesterol levels.
Weight - Being overweight can make your LDL-cholesterol level go up and your HDL level go down.
Physical activity/exercise - Increased physical activity helps to lower LDL- cholesterol and raise HDL-cholesterol levels. It also helps you lose weight.
Mental stress - Several studies have shown that stress raises blood cholesterol levels over the long term. One way that stress may do this is by affecting your habits. For example, when some people are under stress, they console themselves by eating fatty foods. The saturated fat and cholesterol in these foods contribute to higher levels of blood cholesterol.
By David Pittman, Washington Correspondent, MedPage Today