CAMBRIDGE, Mass., May 26, 2015 -- Aegerion Pharmaceuticals, Inc. (Nasdaq:AEGR), a biopharmaceutical company dedicated to the development and commercialization of novel therapies for patients with debilitating rare diseases, today announced the primary endpoint was achieved in the Company's open-label, multicenter study to evaluate the efficacy and safety of lomitapide in nine Japanese patients with homozygous familial hypercholesterolemia (HoFH). The primary endpoint measured mean percent change in low-density lipoprotein cholesterol (LDL-C) at the maximum tolerated dose compared to baseline after 26 weeks of treatment, in combination with other lipid-lowering therapy.
"The data from the Japanese study show consistency with Aegerion's initial global Phase III study of lomitapide, including marked LDL-C reduction and similar safety profile," commented Mark Sumeray, MD, MS, FRCS, Chief Medical Officer of Aegerion. "These data will serve as the basis of our Japanese new drug application for lomitapide in adult HoFH patients which we expect to file late in the fourth quarter of 2015 or early in the first quarter of 2016, with a decision anticipated approximately nine months post-filing. We look forward to the opportunity to present the full data set in the future."
Following the 26 week assessment, patients in the study entered a 30-week safety phase. Each patient will continue receiving the maximum tolerated dose of lomitapide he or she achieved during the efficacy phase for an additional 30 weeks in the safety phase, subject to safety-related dose adjustments. The Company expects to file the NDA in Japan with the 26-week data, and to submit the 56-week data during the review cycle.
HoFH is a serious, rare genetic disease inherited from both parents that impairs the function of the receptor responsible for removing low-density lipoprotein cholesterol (LDL-C or "bad" cholesterol) from the body. A loss of LDL receptor function results in extreme elevation of blood cholesterol levels. HoFH patients often develop premature and progressive atherosclerosis, a narrowing or blocking of the arteries.
Lomitapide, marketed as JUXTAPID® in the U.S., is a microsomal triglyceride transfer protein (MTP) inhibitor that works independently of LDL receptor functionality. JUXTAPID is indicated in the United States 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 safety and effectiveness of lomitapide have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of lomitapide on cardiovascular morbidity and mortality has not been determined.
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.
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, such as nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like-symptoms, 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.
JUXTAPID increases the plasma concentrations of warfarin. Increases or decreases in the dose of JUXTAPID may lead to supra- or subtherapeutic anticoagulation, respectively. 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.
The most common adverse reactions were gastrointestinal, reported by 27 (93%) of 29 patients. Adverse reactions reported by ≥8 (28%) or more patients in the HoFH clinical trial included diarrhea, nausea, vomiting, dyspepsia and abdominal pain. Other common adverse reactions, reported by 5 to 7 (17-24%) patients, included weight loss, abdominal discomfort, abdominal distension, constipation, flatulence, increased ALT, chest pain, influenza, nasopharyngitis, and fatigue.
About Aegerion Pharmaceuticals
Aegerion Pharmaceuticals is a biopharmaceutical company dedicated to the development and commercialization of innovative therapies for patients with debilitating rare diseases. For more information about the company, please visit www.aegerion.com.
This press release contains forward-looking statements, including statements regarding plans for a regulatory filing in Japan, and the potential timing of any such filing. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, among other factors: the risk of unexpected results arising in the course of completion of the Japanese trial; the risk that the Japanese regulatory authorities may require additional data in our filing that we are not able to provide on a timely basis or at all; the risk that the regulatory authorities may not agree with our interpretation of the data from the Japanese HoFH trial; and the risk that, even if we are successful in completing our filing for a new drug application in Japan, Japanese regulatory authorities may not grant marketing approval for lomitapide in the treatment of HoFH; as well as the other risks inherent with development and commercialization of pharmaceuticals.
For additional disclosure regarding these and other risks we face, see the disclosure contained in the "Risk Factors" section of Aegerion's Quarterly Report on Form 10-Q filed on May 8, 2015, and our other public filings with the Securities and Exchange Commission, available on the SEC's website at http://www.sec.gov. We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.