PARIS & CARLSBAD, Calif.--(BUSINESS WIRE)--Genzyme,
a Sanofi company (EURONEXT: SAN and NYSE: SNY), and Isis Pharmaceuticals
Inc. (NASDAQ: ISIS) announced today that two additional analyses from
phase 3 studies of mipomersen were presented at the 79th European
Atherosclerosis Society (EAS) Congress.
“We look forward to the
upcoming filings this year as they will move us closer to our goal of
making mipomersen available to patients who are in the greatest need of
new treatments.”
In a presentation entitled “Mipomersen, A First-in-Class ApoB
Synthesis Inhibitor, Lowers Lp(a) in Patients with Heterozygous Familial
Hypercholesterolemia (HeFH) and High Baseline Lp(a): Results from two
Phase 3 studies,” Elisabeth Steinhagen-Thiessen, M.D., of the Lipid
Ambulatory Clinic, University of Berlin, Germany, focused on the effects
of mipomersen on elevated Lp(a) levels.
Lp(a) is an independent risk factor for heart disease and cardiovascular
events. Elevated Lp(a) levels are recognized to have a strong genetic
component and are particularly common in people with familial
hypercholesterolemia (FH). The EAS consensus panel recommended screening
and treatment for elevated Lp(a) in 2010, and the U.S.-based National
Lipid Association’s expert panel on FH published guidance this year
noting that having elevated Lp(a) levels places FH patients at very high
cardiovascular risk.
Data from two randomized, placebo-controlled phase 3 trials in patients
with HeFH showed that mipomersen reduced Lp(a), LDL-C, and other
measures of atherogenic lipoproteins when added to existing
lipid-lowering therapy. One study included 124 HeFH patients with CAD,
and the other included 58 severe HeFH patients. All of the patients were
already taking a maximally tolerated dose of a statin, as well as
additional lipid-lowering drugs in most cases. Both trials met all of
their primary, secondary and tertiary endpoints. In these trials,
mipomersen decreased LDL-C by 28 and 36 percent compared with increases
of 5 and 13 percent for placebo, respectively (both p<0.001), meeting
primary endpoints in both studies.
In addition to evaluating percent reduction in LDL-C as their primary
endpoints, both trials also evaluated percent reduction in Lp(a) as
tertiary endpoints. Most patients in the two trials (71 and 62 percent)
had elevated Lp(a) levels >20 mg/dl at baseline. Mipomersen decreased
Lp(a) by a median 21 and 39 percent, compared with zero and five percent
for the placebo groups (both p<0.001). Mipomersen lowered Lp(a) by ≥ 50
percent in 22 percent of mipomersen patients across both studies. The
reductions observed were in addition to those achieved with the
patients’ existing therapeutic regimens. Additional detail from these
studies was presented at the European Society of Cardiology’s Congress
last year and the American College of Cardiology’s 60th
Annual Scientific Session this year.
“The findings presented at EAS highlight mipomersen’s potential to
treat the unique needs of patients with severe forms of FH,” said
Vice President and General Manager of Genzyme’s Cardiovascular Business,
Paula Soteropoulos. “Other than apheresis, there is no approved
treatment that addresses the specific challenges faced by severe FH
patients, which include elevated Lp(a) in addition to LDL-C. We
believe mipomersen could play an important role as a targeted treatment
for these patients.”
In a presentation entitled “Mipomersen, an ApoB Synthesis Inhibitor,
Might Reduce Necessity for Lipid Apheresis in CAD,” K.G. Parhofer,
M.D., of Ludwig-Maximilians University, Munich, Germany, focused on
mipomersen’s potential to reduce the necessity for lipid-apheresis by
lowering LDL-C values below thresholds for apheresis eligibility.
Patients with severe forms of FH may be eligible for this treatment, a
dialysis-like procedure where blood is filtered through a machine to
remove excess cholesterol. Country-specific LDL-C thresholds to
determine eligibility for apheresis can range from ≥ 100 mg/dL to ≥ 160
mg/dL. However, many eligible patients are not on apheresis because of
lack of availability, high cost and negative impact on quality of life.
In the phase 3 trial in HeFH patients with CAD, an additional analysis
revealed that mipomersen reduced the percentage of patients with LDL-C
levels ≥ 160 mg/dL by 95 percent (from 39 percent to 2 percent); with
LDL-C levels ≥ 130 mg/dL by 74 percent (from 62 percent to 16 percent);
and with LDL-C levels ≥ 100 mg/dL by 45 percent (from 98 percent to 54
percent). The reductions observed were in addition to those achieved
with the patients’ existing therapeutic regimens. No significant changes
in LDL-C were observed in placebo-treated patients.
“These results suggest that the impact of mipomersen on the treatment
landscape could be quite significant, both in countries such as Germany,
where apheresis is more widely available and the eligibility threshold
is relatively low, and in places like the United States, where apheresis
is not as widely available,” said Dr. Parhofer. “Mipomersen has
the potential to reduce the necessity for apheresis in a considerable
number of patients, and also become an important new treatment option
for those who are eligible for apheresis but cannot access it or
tolerate its impact on their quality of life.”
Genzyme expects to file for EU marketing approval of mipomersen for the
treatment of patients with homozygous (Ho) FH and severe HeFH early in
the third quarter of this year. Genzyme also expects to file for U.S.
approval for the HoFH indication in the second half of this year.
Genzyme and Isis have completed the four phase 3 studies that are
planned to be included in the initial U.S. and EU filings. As previously
reported, the phase 3 study of mipomersen in HoFH patients met its
primary endpoint with 25 percent LDL-C reduction, and the phase 3 study
in patients with high cholesterol at high risk for coronary heart
disease met its primary endpoint with a 37 percent LDL-C reduction.
These studies also met all of their secondary and tertiary endpoints,
which included percent reduction in Lp(a).
In the four phase 3 studies, the most commonly observed adverse events
were injection site reactions and flu-like symptoms. Persistent
elevations in liver transaminases (ALTs) above 3X ULN (three times the
upper limit of normal) were observed in 8 percent of mipomersen-treated
patients across all four studies. Persistent is defined as consecutive
elevations at least one week apart. Mipomersen-treated patients who were
evaluated by MRI had moderate median increases in liver fat. No patients
had changes in other laboratory tests to indicate hepatic dysfunction.
In general, increases in ALT levels and liver fat appeared to be
associated with rapid and larger drops in LDL-C.
“Mipomersen is a great example of the potential antisense technology
holds to address major unmet medical needs,” said President and CEO
of Isis Pharmaceuticals, Stanley T. Crooke. “We look forward to the
upcoming filings this year as they will move us closer to our goal of
making mipomersen available to patients who are in the greatest need of
new treatments.”
About Mipomersen
Mipomersen is a first-in-class apo-B synthesis inhibitor currently in
late-stage development for the reduction of LDL cholesterol (LDL-C). It
is intended to reduce LDL-C by preventing the formation of atherogenic
lipoproteins, the particles that carry cholesterol through the
bloodstream. Mipomersen acts by blocking the production of
apolipoprotein B (apoB), the protein that provides the structural core
for these atherogenic particles, including LDL and lipoprotein-a (Lp(a)).
About Familial Hypercholesterolemia
FH is a genetic disease that results in elevated LDL-C levels and family
patterns of increased risk of premature heart disease and heart
disease-related death. FH patients have inherited abnormalities in liver
cells that are responsible for clearing LDL particles from the blood. FH
is autosomal dominant, which means that all first-degree relatives of FH
patients have a 50 percent chance of having the disease as well, making
early detection through family screening critically important.
The most severe FH patients have LDL-C levels that are two to four times
higher than recommended levels, even when taking multiple
cholesterol-lowering medications. These people, who are characterized as
having severe FH, include: those who have inherited the disease from
both parents (homozygous FH (HoFH)) and those who have inherited it from
only one parent, and have a severe form of the disease (severe
heterozygous FH (severe HeFH)).
For more information about FH and mipomersen, please visit: http://www.multimedianewscenter.com/genzyme/mipomersen-data-portal.
About Genzyme, a Sanofi Company
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 that have provided new hope for patients. The
company’s areas of focus are rare genetic diseases, multiple sclerosis,
cardiovascular disease, and endocrinology. Genzyme is a Sanofi company.
Genzyme’s press releases and other company information are available at www.genzyme.com.
About Sanofi
Sanofi, a global and diversified healthcare leader, discovers, develops
and distributes therapeutic solutions focused on patients’ needs. Sanofi
has core strengths in the field of healthcare with seven growth
platforms: diabetes solutions, human vaccines, innovative drugs, rare
diseases, consumer healthcare, emerging markets and animal health.
Sanofi 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
Sanofi Forward Looking Statement
This press release contains forward-looking statements as defined in
the Private Securities Litigation Reform Act of 1995, as amended.
Forward-looking statements are statements that are not historical facts.
These statements include projections and estimates and their underlying
assumptions, statements regarding plans, objectives, intentions and
expectations with respect to future financial results, events,
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regarding future performance. Forward-looking statements are generally
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management believes that the expectations reflected in such
forward-looking statements are reasonable, investors are cautioned that
forward-looking information and statements are subject to various risks
and uncertainties, many of which are difficult to predict and generally
beyond the control of Sanofi, that could cause actual results and
developments to differ materially from those expressed in, or implied or
projected by, the forward-looking information and statements. 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 any such product
candidates as well as their decisions regarding labeling and other
matters that could affect the availability or commercial potential of
such products candidates, the absence of guarantee that the products
candidates if approved will be commercially successful, the future
approval and commercial success of therapeutic alternatives, the Group’s
ability to benefit from external growth opportunities as well as those
discussed or identified in the public filings with the SEC and the AMF
made by Sanofi, including those listed under “Risk Factors” and
“Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s
annual report on Form 20-F for the year ended December 31, 2010. Other
than as required by applicable law, Sanofi does not undertake any
obligation to update or revise any forward-looking information or
statements.
Isis Forward Looking 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.