FDA Approves New Treatment for HoFH

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On Dec 24th, 2012 Aegerion Pharmaceuticals, Inc. announced that the U.S. Food & Drug Administration (FDA) approved new treatment for Homozygous Familial Hypercholesterolemia (HoFH) called JUXTAPID™ (lomitapide). The capsules are intended as an adjunct to a low-fat diet and other cholesterol-lowering treatments (such as LDL-apheresis). Their purpose is to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B) and non- high-density-lipoprotein cholesterol (non-HDL) in individuals with HoFH. It has not yet been established whether JUXTAPID is safe to use for children with Homozygous FH. It is also not yet known whether it is effective for patients with Heterzygous FH.

The Chief Executive Officer at Aegerion. Marc Beer, commented “We are excited that JUXTAPID will become a new treatment option for patients with HoFH… The approval of our first product also marks an important corporate milestone for Aegerion and reflects our commitment to help patients in need.”

HoFH is a severe, rare form of the genetic disorder FH. It is found in individuals who have inherited the FH gene from both parents. As a result, the function of the receptor responsible for removing LDL-C (“bad” cholesterol) from the body is impaired. This causes the cholesterol in the blood to reach exceedingly high levels. One of the more often observed effects in individuals with HoFH is premature and progressive atherosclerosis, a narrowing or blocking of the arteries.

Our foundation’s President, Katherine Wilemon comments, “The FDA approval of JUXTAPID is a major step forward for HoFH patients and their families, who have long been waiting for new therapies. New treatments, combined with further understanding and awareness of this disease, can bring much needed hope to the HoFH community.”

It is important to note that JUXTAPID awaits more post-approval studies and observation as its safety is not yet completely determined.

Please refer to the information provided below by Aegerion for Important Safety Information about JUXTAPID, including the Boxed Warning, Contraindications and Warnings and Precautions.

Because of the risk of liver toxicity, JUXTAPID is available only through a restricted program called the JUXTAPID Risk Evaluation and Mitigation Strategy (REMS) Program. Aegerion will certify all health care providers who prescribe JUXTAPID and the pharmacies that will dispense the medicine.

As part of the planned launch of JUXTAPID, the company has developed a comprehensive support services program for patients and their healthcare providers. For more information, call this toll-free number: 1-85JUXTAPID.

Important Safety Information, including BOXED WARNING which states:

WARNING: RISK OF HEPATOTOXICITY

JUXTAPID can cause elevations in transaminases. In the JUXTAPID clinical trial, 10 (34%) of the 29 patients treated with JUXTAPID had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase.

JUXTAPID also increases hepatic fat, with or without concomitant increases in transaminases. The median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy. Hepatic steatosis associated with JUXTAPID treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.

Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended. During treatment, adjust the dose of JUXTAPID if the ALT or AST are ≥3x ULN. Discontinue JUXTAPID for clinically significant liver toxicity.

Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the JUXTAPID REMS Program.

CONTRAINDICATIONS

Pregnancy
Concomitant administration of moderate or strong CYP3A4 inhibitors
Moderate or severe hepatic impairment or active liver disease including unexplained persistent elevations of serum transaminases

WARNINGS AND PRECAUTIONS

JUXTAPID can cause elevations in transaminases and hepatic steatosis. Although cases of hepatic failure have not been reported, there is concern that JUXTAPID could induce steatohepatitis, which can progress to cirrhosis over several years. Modify the dose of JUXTAPID if elevations of transaminases are observed and discontinue JUXTAPID for persistent or clinically significant elevations. If transaminase elevations are accompanied by clinical symptoms of liver injury, increases in bilirubin ≥2x ULN, or active liver disease, discontinue treatment with JUXTAPID and identify the probable cause. Use JUXTAPID with caution when co-administered with agents known to be hepatotoxic. Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury.

Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment. During the first year, measure liver-related tests (ALT and AST at a minimum) prior to each increase in dose or monthly, whichever occurs first. After the first year, do these tests at least every 3 months and before any increase in dose.

Females of reproductive potential should have a negative pregnancy test before starting JUXTAPID and should use effective contraception during therapy with JUXTAPID.

Given its mechanism of action in the small intestine, JUXTAPID may reduce the absorption of fat-soluble nutrients. Patients treated with JUXTAPID should take daily supplements that contain 400 international units vitamin E and at least 200 mg linoleic acid, 210 mg alpha-linolenic acid (ALA), 110 mg eicosapentaenoic acid (EPA), and 80 mg docosahexaenoic acid (DHA).

Gastrointestinal adverse reactions are common and may lead to treatment discontinuation. To reduce the risk of gastrointestinal adverse reactions, patients should adhere to a low-fat diet supplying less than 20% of energy from fat and the dosage of JUXTAPID should be increased gradually.

Combination with CYP3A4 inhibitors increases exposure to lomitapide. Strong and moderate CYP3A4 inhibitors should not be used with JUXTAPID. JUXTAPID dosage should not exceed 30 mg daily when used concomitantly with weak CYP3A4 inhibitors.

Due to risk of myopathy associated with simvastatin or lovastatin, doses of these agents should be limited when co-administered with JUXTAPID.

Patients taking warfarin should undergo regular monitoring of the INR, especially after any changes in JUXTAPID dosage.

Avoid use of JUXTAPID in patients with rare hereditary disorders of galactose intolerance.

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