Aegerion Pharmaceuticals said today that the FDA had approved lomitapide (Juxtapid) to help further lower cholesterol in patients with homozygous familial hypercholesterolemia. The approval comes with a box warning about the risk of hepatotoxicity and a Risk Evaluation and Mitigation Strategy (REMS) Program which will require certification of health care providers and pharmacies before the drug can be prescribed and dispensed. The drug is expected to cost between $200,000-$300,000 per year.
The novel drug, which is a microsomal triglyceride transfer protein inhibitor is indicated, according to the label, “as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH)” The label notes that the safety and effectiveness of the drug has not been established in hypercholesterolemia patients who do not have homozygous FH and that the effect of the drug on cardiovascular morbidity and mortality has not been determined.
Click here to read the press release from Aegerion…
The FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 13-2 to recommend approval of Aegerion Pharmaceuticals’ cholesterol-lowering drug lomitapide for use in patients with homozygous familial hypercholesterolemia (FH).
The lopsided vote does not completely reflect the views of many of the panel members, who expressed considerable concern that the drug might be used in lower risk populations, in particular, patients with heterozygous FH. The committee also expressed concern about the use of lomitapide in children with homozygous FH, since they were not included in clinical trials, but might be considered candidates for therapy in clinical practice.
Panel members appeared to largely agree with one panel member, who explained that his yes vote was “specific for this condition” (homozygous FH) only. He said he could accept the “trade-off between a near-certain early demise versus the possibility of liver disease.”
Aegerion estimates that there are about 6,000 homozygous FH patients in the US and Europe.
The committee expressed support for the FDA’s proposed Risk Evaluation and Mitigation Strategy (REMS) that would limit access to the drug to medically appropriate patients and to provide education to prescribers about how to use lomitapide, how to prevent liver damage, and how to monitor patients during treatment. The REMS would require special certification for health care professionals and pharmacies that prescribe and dispense the drug.
On Thursday the same committee will meet to discuss a similar indication for Genzyme’s mipomersen injection. Following the release of a highly critical FDA review, many observers believe the mipomersen panel will be much more contentious.
FDA reviewers have raised no new concerns about lomitapide ahead of a Wednesday meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. The FDA today released briefing documents that evaluate the new drug application (NDA) for lomitapide capsules, the microsomal triglyceride transfer protein (MTP) inhibitor from Aegerion Pharmaceuticals for use as an adjunct to a low-fat diet and other lipid-lowering drugs with or without LDL apheresis to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and triglycerides in patients with homozygous familial hypercholesterolemia. (On Thursday the same committee will meet to discuss a similar indication for Genzyme’s mipomersen injection. Briefing documents for that meeting will be released on Tuesday.)
The reviewers concluded that lomitapide was effective in lowering LDL cholesterol by about 40%. The drug also effectively reduced total cholesterol, apoB, triglyceride, non-HDL, VLDL, and Lp(a) levels. Lomitapide also lowered potentially beneficial HDL and Apo A1 levels. The reviewers said that “the clinical consequences, if any, of these changes are unknown.”
The committee will likely focus on side effects and safety issues related to lomitapide. Gastrointestinal side effects are common with the drug. More troubling are concerns about possible liver damage associated with the drug. In the pivotal trial 38% of the patients had ALT elevations greater than three times the upper limit of normal, and 24% had elevations five times the ULN. Most patients in the trials also had significant elevations in hepatic fat. The reviewers also noted that lomitapide might induce deficiencies in fat-soluble nutrients.
To address the safety issues related to lomitapide the FDA will ask the committee to evaluate a Risk Evaluation and Mitigation Strategies (REMS) that would limit access to the drug to medically appropriate patients and to provide education to prescribers about how to use lomitapide, how to prevent liver damage, and how to monitor patients during treatment. The REMS would require special certification for health care professionals and pharmacies that prescribe and dispense the drug.