Study Meets Primary Endpoint with 28 Percent LDL-C Reduction
CAMBRIDGE, Mass. & CARLSBAD, Calif.–(Business Wire)–
Genzyme Corp. (NASDAQ: GENZ) and Isis Pharmaceuticals Inc. (NASDAQ: ISIS)
announced that data from the phase 3 study of mipomersen in patients with
heterozygous familial hypercholesterolemia (heFH) were presented today at the
European Society of Cardiology`s Congress 2010 in Stockholm, Sweden. The study
met its primary endpoint with a 28 percent reduction in LDL-cholesterol,
compared with an increase of 5 percent for placebo (p<0.001). The trial also met
all of its secondary and tertiary endpoints. Frequently observed adverse events
were injection site reactions, flu-like symptoms and elevations in liver
transaminases, as seen in other mipomersen studies.
This double-blind, placebo-controlled phase 3 study was designed to test the
efficacy and safety of adding mipomersen to stable lipid-lowering therapy.
Patients were randomized 2:1 to receive a 200 mg dose of mipomersen or placebo
weekly for 26 weeks. The trial included 124 adult heFH patients at 26 sites in
the United States and Canada. All of the patients had pre-existing coronary
artery disease and LDL-C levels greater than 100 mg/dL, and were taking a
maximally tolerated dose of a statin, as well as additional lipid-lowering drugs
in most cases. Prior to study enrollment, 78 percent of patients had previously
experienced at least one cardiovascular event and 49 percent had more than one
previous cardiovascular event.
Patients treated with mipomersen had an average LDL-C at baseline of 150 mg/dL.
These patients had an average LDL-C level of 104 mg/dL at the end of the study.
Forty-five percent of the mipomersen-treated patients achieved LDL-C levels of
less than 100 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 therapeutic regimens.
The trial met all of its secondary and tertiary endpoints. Patients treated with
mipomersen experienced a 26 percent reduction in apolipoprotein B compared with
a 7 percent increase for placebo; a 19 percent reduction in total cholesterol
compared with a 4 percent increase for placebo; and a 25 percent reduction in
non-HDL cholesterol compared with a 4 percent increase for placebo (all
Reductions were observed in other atherogenic lipids, including Lp(a) by 21
percent compared with no change for placebo (p<0.001). Apo B and Lp(a) are both
generally accepted risk factors for cardiovascular disease. Study results are
based on an intent-to-treat analysis (full analysis set).
“Having these data presented is a great milestone for the mipomersen program,”
said Paula Soteropoulos, vice president and general manager of Genzyme`s
cardiovascular business. “The data underscore our belief that mipomersen has the
potential to help those familial hypercholesterolemia patients who are `left
behind` by current therapies, and are in need of new treatment options.”
As seen in other mipomersen studies, the most commonly observed adverse events
were injection site reactions (93 percent for mipomersen compared with 42
percent for placebo) and flu-like symptoms (49 percent for mipomersen compared
with 32 percent for placebo).
All 41 patients treated with placebo completed treatment. Of the 83 patients
treated with mipomersen, 73 completed treatment; nine of the discontinuations
were related to adverse events, the nature of which was generally similar to
previous studies. Reasons for withdrawal from the mipomersen group were:
elevations in liver transaminases (3), injection site reactions (2), non-cardiac
chest pain (2), injection site reactions and flu-like symptoms (1), and
In this study, elevations in liver transaminases (ALTs) in patients treated with
mipomersen were observed that were generally similar in character with those
seen in other studies. Six mipomersen-treated patients (7 percent) 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 modest change in liver fat from baseline
(median increase of 4.9 percent), compared with the placebo-treated patients
(median increase of 0.4 percent). In general, increases in liver transaminases
and liver fat appeared to be associated with the greatest reductions of LDL
cholesterol. No patients, including those who discontinued the study, had
changes in other laboratory tests to indicate hepatic dysfunction, and there
were no Hy`s Law cases.
“In all four of the phase 3 studies we have completed, we have seen consistent
and robust reductions in LDL cholesterol and other atherogenic lipids that
support our plan to initially target homozygous and severe heterozygous familial
hypercholesterolemia patients,” said Isis Pharmaceuticals Chairman and CEO
Stanley T. Crooke. “We are excited by these positive phase 3 results and look
forward to working with Genzyme to bring mipomersen to patients who are in need
of a new and novel lipid-lowering agent.”
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`s initial U.S. and E.U. regulatory filings for mipomersen will seek
marketing approval for the treatment of patients with homozygous FH (hoFH).
These initial filings may also include patients with severe heFH. In the first
half of 2011, Genzyme expects to submit the initial U.S. and E.U. filings, and
to have made progress toward filing in other major international markets.
Genzyme and Isis have completed all four phase 3 studies planned to support the
initial filings. As previously reported, the phase 3 study of mipomersen in hoFH
patients met its primary endpoint with 25 percent LDL-C reduction, and results
were presented at last year`s American Heart Association meeting. Genzyme and
Isis announced top-line results of the phase 3 study in heFH patients in
February. The companies last month reported that the phase 3 studies of
mipomersen in severe hypercholesterolemia and high-risk patients met their
primary endpoints with 36 and 37 percent LDL-C reductions. These four studies
will be included in the initial filings. In addition, studies are ongoing and
planned to evaluate alternative dosing regimens.
About Familial Hypercholesterolemia
FH is one of the most common genetic disorders, and results in elevated LDL
cholesterol levels. FH patients have inherited abnormalities in liver cells that
are responsible for clearing LDL-C from the blood. These patients experience a
markedly increased risk of premature cardiovascular disease (CVD) and
There are two forms of FH: homozygous (hoFH), where a defective gene is
inherited from both parents, or heterozygous (heFH), where a defective gene is
inherited from only one parent. HoFH is a very rare condition estimated to
affect approximately one in a million people worldwide. HeFH is a more common
form of the disorder, with a prevalence of approximately one in 500.
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 1981, the company has grown from a small start-up to a diversified
enterprise with more than 12,000 employees in locations spanning the globe and
2009 revenues of $4.5 billion. In 2010, Genzyme was named to the Fortune 500.
With many established products and services helping patients in 100 countries,
Genzyme is a leader in the effort to develop and apply the most advanced
technologies in the life sciences. The company’s products and services are
focused on rare inherited disorders, kidney disease, orthopaedics, cancer,
transplant, and immune disease. Genzyme’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
Genzyme`s press releases and other company information are available at
www.genzyme.com and by calling Genzyme`s investor information line at
1-800-905-4369 within the United States or 1-678-999-4572 outside the United
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 23 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 is the owner or exclusive licensee of approximately 1,600 issued patents
worldwide. 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, its safety profile, the
expected timing of regulatory filings in the U.S. and E.U., and the studies that
are expected to form a 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
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; the actual efficacy and safety of mipomersen including, without
limitation, the effects of elevations in liver transaminases; 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 Quarterly Report on Form 10-Q for the period ended June
30, 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.
Genzyme is a registered trademark of Genzyme Corporation. All rights reserved.
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 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, 2009 and its most
recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of
these 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.
Erin Emlock, 617-768-6923
Leah Monteiro, 617-768-6602
Amy Blackley, Ph.D., 760-603-2772
Kristina Lemonidis, 760-603-2490
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