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
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