October 18th, 2012

FDA Reviewers Recommend Approval of Lomitapide for Homozygous Familial Hypercholesterolemia

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-2 on Wednesday 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 6000 homozygous FH patients in the U.S. 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.

One Response to “FDA Reviewers Recommend Approval of Lomitapide for Homozygous Familial Hypercholesterolemia”

  1. Uffe Ravnskov, MD, PhD says:

    A relevant question is, whether cholesterol lowering is the right way to treat people with FH, because several cohort studies of people with FH have shown that the risk of CHD is the same, whether their cholesterol is only a little higher than normal or it is 2-3 times higher (1-7). Another striking observation is that even in homozygous FH, the cerebral arteries are not more atherosclerotic than in normal people (8,9).

    Then what causes atherosclerosis in FH? This is a relevant question, and there is a likely answer. For instance, in a study of 61 people with FH Sugrue et al. found that plasma fibrinogen and factor VIII were significantly higher in the 32 patients with CHD than in the 29 patients without, whereas there were no significant differences in serum lipid concentrations (1). In a more recent study of 1940 people with FH Jansen et al. found that G20210A polymorphism in the prothrombin gene was strongly associated with CHD risk (10).

    Evidently some of the people with FH have inherited other genetic aberrations of more importance than hypercholesterolemia. Hypercoagulability may explain why atherosclerosis in FH is located mainly to the arteries that are exposed to mechanical forces, such as the arteries of the heart and the legs, while premature atherosclerosis is absent in the arteries of the brain. Maybe it would be a better idea to measure these factors in all people with FH and in case they are elevated, treat them with warfarin.

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    7. Jansen AC et al. Arterioscler Thromb Vasc Biol 2005;25:1475-81.
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    9. Rodriguez G et al. Stroke 1994;25:831-6.
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