CAMBRIDGE, Mass. & CARLSBAD, Calif.--(BUSINESS WIRE)--Genzyme
Corp., a subsidiary of sanofi-aventis Group (EURONEXT: SAN and NYSE:
SNY), and Isis Pharmaceuticals Inc. (NASDAQ: ISIS) announced today that
data from two phase 3 studies of mipomersen in patients who had high
cholesterol levels while on lipid-lowering therapy were presented at the
American College of Cardiology’s 60th Annual Scientific
Session.
“These are patients who are on maximally tolerated doses
of currently available treatments, and still very far from appropriate
target goals, leaving them at high risk of cardiovascular events. These
patients have a need for additional lipid lowering, which mipomersen
could potentially provide.”
In the study in patients with severe heterozygous familial
hypercholesterolemia (heFH), mipomersen reduced LDL-C, the primary
endpoint, by 36 percent compared with a 13 percent increase for placebo
(p<0.001). This study, which was presented today by Jean-Claude Tardif,
M.D., of the Montreal Heart Institute, Montreal, Canada, also met each
of its secondary endpoints. Frequently observed adverse events were
injection site reactions, flu-like symptoms and elevations in liver
transaminases, as seen in previous studies.
"We are excited about the potential of mipomersen to help these
patients, who are in great need of new treatment options,” said Paula
Soteropoulos, vice president and general manager of Genzyme’s
cardiovascular business. "We are committed to advancing our mipomersen
development and commercialization plan to bring this uniquely targeted
treatment to these patients, who are left behind by current treatments."
This double-blind, placebo-controlled trial included 58 patients with
severe heFH, who were already taking maximally tolerated lipid-lowering
medications. Severe heFH patients were defined as those who had LDL-C
levels ≥ 300 mg/dL or those who had LDL-C levels ≥ 200 mg/dL with
coronary heart disease (CHD) or other forms of clinical atherosclerotic
disease. Patients were randomized 2:1 to receive a self-administered 200
mg subcutaneous injection of mipomersen or placebo weekly for 26 weeks.
This study was conducted at 26 sites in North America, Europe and South
Africa.
Patients treated with mipomersen had an average LDL-C at baseline of 276
mg/dL. At the end of the trial, these patients had an average LDL-C
level of 175 mg/dL, representing an average LDL-C reduction of 101 mg/dL
(36 percent). The reductions observed in the study were in addition to
those achieved with the patients’ existing maximally tolerated
lipid-lowering regimens.
Patients treated with mipomersen also experienced reductions in other
atherogenic lipids, including: a 36 percent reduction in apolipoprotein
B (apo-B) compared with an 11 percent increase for placebo; a 33 percent
reduction in lipoprotein a (Lp(a)) compared with a 1 percent reduction
for placebo; a 34 percent reduction in non-HDL-cholesterol compared with
a 14 percent increase for placebo; and a 28 percent reduction in total
cholesterol compared with an 11 percent increase for placebo (all
p<0.001). Study results are based on an intent-to-treat analysis (full
analysis set).
Of the 39 patients treated with mipomersen, 27 completed treatment; of
the 19 patients treated with placebo, 18 completed treatment. Eight of
the discontinuations in the mipomersen group were reported as being
related to adverse events, the nature of which was generally similar to
previous studies. The placebo discontinuation was reported as being
related to an adverse event. The most common adverse events were
injection site reactions (90 percent mipomersen; 32 percent placebo) and
flu-like symptoms (46 percent mipomersen; 21 percent placebo.) There was
one death in the study due to acute coronary syndrome in a patient
treated with mipomersen.
Elevations in liver transaminases (ALTs) in patients treated with
mipomersen were observed that were generally similar in character with
those seen in other studies. In this study, 15 percent of mipomersen
patients had persistent ALT elevations above 3X ULN (three times the
upper limit of normal) during the treatment period. Persistent is
defined as consecutive elevations at least one week apart. No patients
had changes in laboratory tests indicative of clinically significant
hepatic dysfunction, and there were no Hy’s Law cases. In general,
increases in ALT levels appeared to be associated with rapid and larger
drops in LDL-C.
“There remains a significant unmet medical need for new lipid-lowering
therapies for patients such as those included in this study,” said Mary
McGowan, M.D., of the Concord Hospital Cholesterol Treatment Center,
Concord, N.H. “These are patients who are on maximally tolerated doses
of currently available treatments, and still very far from appropriate
target goals, leaving them at high risk of cardiovascular events. These
patients have a need for additional lipid lowering, which mipomersen
could potentially provide.”
Results of a phase 3 study of mipomersen in patients with high
cholesterol at high risk for CHD were also presented in a poster at ACC.
In this study, mipomersen reduced LDL-C, the primary endpoint, by 37
percent compared with a 5 percent reduction for placebo (p<0.001). The
study, which was presented by William Cromwell, M.D., of the
Presbyterian Cardiovascular Institute, Charlotte, N.C., also met each of
its secondary endpoints.
This double-blind, placebo-controlled trial included 158 patients with
hypercholesterolemia (LDL-C ≥ 100 mg/dL) and at high risk of developing
CHD who were taking a maximally tolerated dose of a statin. Patients
were randomized 2:1 to receive a self-administered 200 mg subcutaneous
injection of mipomersen or placebo weekly for 26 weeks.
Patients treated with mipomersen had an average LDL-C at baseline of 123
mg/dL. At the end of the study, these patients had an average LDL-C
level of 75 mg/dL, representing an average LDL-C reduction of 48 mg/dL
(37 percent). Half of the mipomersen-treated patients achieved LDL-C
levels of less than 70 mg/dL, a recognized treatment goal for high-risk
patients. The reductions observed in the study were in addition to those
achieved with the patients’ existing maximally tolerated statin
regimens. Patients treated with mipomersen also experienced
statistically significant reductions in apo-B, Lp(a),
non-HDL-cholesterol and total cholesterol. Study results are based on an
intent-to-treat analysis (full analysis set).
Of the 105 patients treated with mipomersen, 60 completed treatment; of
the 53 patients treated with placebo, 44 completed treatment. Twenty-six
of the discontinuations in the mipomersen group were reported as being
related to adverse events, the nature of which was generally similar to
previous studies. Two of the discontinuations in the placebo group were
reported as being related to adverse events. The most common adverse
events were injection site reactions and flu-like symptoms. There was
one death during the on-treatment study period due to acute myocardial
infarction in a patient treated with placebo. During the post-treatment
follow-up period, one patient died due to liver failure, acetaminophen
toxicity, pneumonia and myocardial infarction 149 days after receiving
the last dose of mipomersen treatment.
Elevations in ALTs in patients treated with mipomersen were observed
that were generally similar in character with those seen in other
studies. In this study, 10 percent of patients had persistent ALT
elevations above 3X ULN during the treatment period. Persistent is
defined as consecutive elevations at least one week apart. As measured
by MRI, mipomersen-treated patients had a moderate increase in liver fat
from baseline compared with placebo-treated patients. In general,
increases in liver transaminases and liver fat appeared to be associated
with the greatest reductions of LDL-C, and in the six-month follow-up
period after treatment was discontinued, returned toward baseline along
with all lipids, including LDL-C, apo-B and Lp(a).
About Mipomersen
Mipomersen is a first-in-class apo-B synthesis inhibitor currently in
late-stage development. It is intended to reduce LDL-C by preventing the
formation of atherogenic lipids. It acts by decreasing the production of
apo-B, which provides the structural core for all atherogenic lipids,
including LDL-C, which carry cholesterol through the bloodstream.
Genzyme and Isis have completed the four phase 3 studies that are
planned to be included in the initial U.S. and EU filings for marketing
approval of mipomersen. As previously reported, the phase 3 study of
mipomersen in homozygous (ho) FH patients met its primary endpoint with
25 percent LDL-C reduction, and the phase 3 study in heFH patients met
its primary endpoint with a 28 percent LDL-C reduction.
Genzyme expects to file for EU marketing approval of mipomersen for the
treatment of patients with hoFH and severe heFH in the first half of
this year. Genzyme also expects to file for U.S. approval for the hoFH
indication in the second half of this year.
For more information about FH and mipomersen, please visit:
http://www.multimedianewscenter.com/genzyme/mipomersen-data-portal
About Genzyme
One of the world's leading biotechnology companies, Genzyme is dedicated
to making a major positive impact on the lives of people with serious
diseases. Since its founding in 1981, the company has introduced
breakthrough treatments across several areas of medicine that have
provided new hope for patients. Today, approximately 10,000 Genzyme
employees serve patients in nearly 100 countries.
Genzyme's products are focused on rare inherited disorders, kidney
disease, orthopaedics, cancer, transplant, and immune disease. The
company's commitment to innovation continues today with a substantial
development program focused on these fields, as well as cardiovascular
disease, neurodegenerative diseases, and other areas of unmet medical
need. Genzyme is part of the sanofi-aventis Group.
About sanofi-aventis
Sanofi-aventis, a leading global pharmaceutical company, discovers,
develops and distributes therapeutic solutions to improve the lives of
everyone. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New
York (NYSE: SNY).
About Isis Pharmaceuticals, Inc.
Isis is exploiting its expertise in RNA to discover and develop novel
drugs for its product pipeline and for its partners. The Company has
successfully commercialized the world's first antisense drug and has 24
drugs in development. Isis' drug development programs are focused on
treating cardiovascular, metabolic, and severe neurodegenerative
diseases and cancer. Isis' partners are developing antisense drugs
invented by Isis to treat a wide variety of diseases. Isis and Alnylam
Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company
focused on the discovery, development and commercialization of microRNA
therapeutics. Isis also has made significant innovations beyond human
therapeutics resulting in products that other companies, including
Abbott, are commercializing. As an innovator in RNA-based drug discovery
and development, Isis has designed and executed a patent strategy that
has provided the Company with strong and extensive protection for Isis’
drugs and technology. Additional information about Isis is available at www.isispharm.com.
Genzyme Safe Harbor Statement
This press release contains forward-looking statements regarding
Genzyme’s business plans and strategies regarding mipomersen including,
without limitation, statements about its potential uses, the expected
timing of regulatory filings in the U.S. and E.U. and the studies that
are expected to form the basis of the regulatory filings. These
statements are subject to risks and uncertainties that could cause
actual results to differ materially from those forecasted. These risks
and uncertainties include, among others: that regulatory authorities
determine additional clinical studies of mipomersen are needed to
support a 2011 filing; that Genzyme is unable to reach agreement with
regulatory authorities regarding additional clinical studies; that
Genzyme is unable to continue to support its clinical and other
development efforts related to mipomersen; that regulatory authorities
determine mipomersen’s safety profile does not support approval for
treatment of any or all of the targeted population; and the risks and
uncertainties described in Genzyme's SEC reports filed under the
Securities Exchange Act of 1934, including the factors discussed under
the caption "Risk Factors" in Genzyme's Annual Report on Form 10-K for
the period ended December 31, 2010. Genzyme cautions investors not to
place undue reliance on the forward-looking statements contained in this
press release. These statements speak only as of the date of this press
release and Genzyme undertakes no obligation to update or revise the
statements.
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Private Securities Litigation Reform Act of 1995, as amended.
Forward-looking statements are statements that are not historical facts.
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These risks and uncertainties include among other things, the
uncertainties inherent in research and development, future clinical data
and analysis, including post marketing, decisions by regulatory
authorities, such as the FDA or the EMA, regarding whether and when to
approve any drug, device or biological application that may be filed for
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Forward-Looking Statements” in sanofi-aventis’ annual report on Form
20-F for the year ended December 31, 2010. Other than as required by
applicable law, sanofi-aventis does not undertake any obligation to
update or revise any forward-looking information or statements.
Isis Safe Harbor Statement
This press release includes forward-looking statements regarding Isis’
collaboration with Genzyme Corporation, its financial and business
development activities, and the development, activity, therapeutic and
commercial potential and safety of mipomersen in treating patients with
high cholesterol. Any statement describing Isis’ goals, expectations,
financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk statement.
Such statements are subject to certain risks and uncertainties,
particularly those inherent in the process of discovering, developing
and commercializing drugs that are safe and effective for use as human
therapeutics, and in the endeavor of building a business around such
drugs. Isis’ forward-looking statements also involve assumptions that,
if they never materialize or prove correct, could cause its results to
differ materially from those expressed or implied by such
forward-looking statements. Although Isis’ forward-looking statements
reflect the good faith judgment of its management, these statements are
based only on facts and factors currently known by Isis. As a result,
you are cautioned not to rely on these forward-looking statements. These
and other risks concerning Isis’ programs are described in additional
detail in Isis’ annual report on Form 10-K for the year ended December
31, 2010, which is on file with the SEC. Copies of this and other
documents are available from the Company.
Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals,
Inc. Regulus Therapeutics is a trademark of Regulus Therapeutics Inc.