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January 10, 2007
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, NJ (January 10, 2007) – 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®)*,
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.”
* Zetia®
(ezetimibe) is a registered trademark of MSP Singapore
Company, LLC.
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.
Contact
Kate Childress, Vox Medica
Health-care Public Relations Group
(t) 215-238-8500 ext 1107
(e)
kchildress@voxmedica.com
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