New England Journal of Medicine Reports Aegerion's Lead Compound Reduces LDL By 51% in Patients With a Severe Form of Hypercholesterolemia

Phase III Trials Planned in 2007 for Homozygous Familial Hypercholesterolemia Patient Population

BRIDGEWATER, N.J., Jan. 10, 2007 /PRNewswire/ -- Aegerion Pharmaceuticals, Inc., a specialty pharmaceutical company focused on the treatment of cardiovascular and metabolic diseases, today announced the publication of positive results from a second Phase II clinical trial of its lead cholesterol-lowering compound AEGR-733 in the January 11, 2007 issue of the New England Journal of Medicine.

"The results of this study suggest that microsomal triglyceride transfer protein (MTP) inhibition with AEGR-733 is a highly effective and potentially promising agent to treat these high-risk, hard-to-treat patients, for whom there are few effective treatment options.  It may also have applicability in a much broader population of patients - those who are not sufficiently clinically responsive to standard therapy or are intolerant of statins," said Daniel J. Rader, MD, Director of the Clinical and Translational Research Center at the University of Pennsylvania School of Medicine and the lead investigator for this study. "There are many patients who are not able to get to recommended levels with the therapies that are available today," he added.

 The results demonstrate that AEGR-733 (previously known as BMS-201038) reduced the levels of low-density lipoprotein (LDL) or "bad cholesterol" by a remarkable 51% from baseline in subjects with homozygous familial hypercholesterolemia (FH), a genetic condition characterized by dangerously high LDL-C levels.  AEGR-733 was also effective in reducing total cholesterol levels by 58%, triglyceride levels by 65%, and apolipoprotein B levels by 56% from baseline.

 Researchers at the University of Pennsylvania School of Medicine conducted a dose-escalation study examining the efficacy, safety, and tolerability of AEGR-733 in 6 patients with homozygous FH who were titrated to the study's highest dose.  Patients received AEGR-733 at 4 different doses, each for 4 weeks, and returned for a final visit after an additional 4-week drug washout period.  Analysis of lipid levels, safety laboratory analyses, and magnetic resonance imaging of the liver for hepatic fat content were performed throughout the study. The most common adverse events were loose stool/diarrhea.  Elevation of liver transaminase levels and accumulation of hepatic fat were seen in some, but not all, of the study patients.

As a result of their dangerously high LDL-C levels, patients with homozygous FH are at an increased risk of premature cardiovascular disease and death, and existing agents are minimally effective in reducing LDL-C in this population.  AEGR-733 is an investigational MTP inhibitor, a new class of cholesterol-lowering agents that inhibit the protein that produces low-density lipoprotein.  AEGR-733 is expected to enter Phase III trials later this year with continued development of the compound in the homozygous FH population.  A second developmental pathway will focus on the treatment of the broader hypercholesterolemic population, who are either unable to achieve recommended cholesterol levels on currently available therapies or cannot tolerate statin therapy.

Results from an earlier Phase II trial, involving lower doses of AEGR-733 alone or in combination with ezetimibe (Zetia(R))*, a cholesterol absorption inhibitor, in a hypercholesterolemic patient population were presented at the American Heart Association Scientific Sessions Conference in November 2006.  Patients treated with a combination of AEGR-733 plus ezetimibe achieved a 35% reduction in LDL-C after 4 weeks.  There was no difference in discontinuation rates between the patients who received AEGR-733 in combination with ezetimibe or ezetimibe alone.  In addition, AEGR-733 alone was shown to be effective in reducing LDL-C.  Ongoing Phase II development is aimed at continuing to explore AEGR-733 in this broader hypercholesterolemic population.

"We are extremely encouraged by the results of this trial, as it provides a second proof of concept of the potential of AEGR-733 to treat patients who are not able to reduce their cholesterol to recommended levels with currently available agents," said Jerry Wisler, President and Chief Executive Officer of Aegerion Pharmaceuticals.  "We are excited about the potential of AEGR-733, especially as guidelines for target cholesterol levels continue to become more aggressive.  Aegerion's approach is to develop compounds that complement existing therapies to help patients get to their goals.  AEGR-733 shows promise as a potential new treatment for high cholesterol. 

About AEGR-733

AEGR-733 is a novel proprietary MTP inhibitor under development for the treatment of dyslipidemia (abnormal lipid levels in the bloodstream).  Inhibiting the MTP enzyme reduces blood levels of cholesterol and triglyceride by limiting the production of lipoproteins from the intestine and liver.  In the United States alone, nearly 100 million adults have total blood cholesterol values of 200 mg/dL and higher, and 34.5 million have levels of 240 and above.  Current guidelines recommend that appropriate LDL levels in patients at high risk of cardiovascular disease should be less than 100 mg/dL, or below 70 mg/dL for very high-risk patients.  Under these guidelines, 36 million people would be eligible for treatment.  Standard therapies, such as statins and cholesterol absorption inhibitors, do not effectively lower LDL-C to target levels in a significant number of patients.  

About Aegerion Pharmaceuticals, Inc.

Aegerion Pharmaceuticals, Inc. is a privately held specialty pharmaceutical company with a highly experienced senior management team.  The company is focused on the development and commercialization of pharmaceuticals to treat cardiovascular and metabolic disease.  Its most advanced products are MTP inhibitors which have demonstrated significant clinical effects in Phase II trials in patients with various forms of hyperlipidemia and whose cholesterol levels remain uncontrolled on currently available dyslipidemia therapies.  MTP inhibitors represent a potentially new therapeutic approach for hyperlipidemia and a significant commercial opportunity for Aegerion Pharmaceuticals, Inc.

CONTACT:  Jeff McLaughlin, Vox Medica, +1-215-925-9901 ext 1416, jmclaughlin@voxmedica.com, for Aegerion Pharmaceuticals, Inc.Web site:  http://www.aegerion.com

Posted: January 2007

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