CAMBRIDGE, Mass. & CARLSBAD, Calif.--(BUSINESS WIRE)--Genzyme
Corp. (NASDAQ: GENZ) and Isis
Pharmaceuticals Inc. (NASDAQ: ISIS) today announced that the phase 3
study of mipomersen in patients with heterozygous familial
hypercholesterolemia (heFH) met its primary endpoint with a highly
statistically significant 28 percent reduction in LDL-cholesterol after
26 weeks of treatment, compared with an increase of 5 percent for
“Mipomersen has again delivered positive results with this second phase
3 study, and continues to make progress toward the market”
All of the 124 patients in the study had pre-existing coronary artery
disease, were taking a maximally tolerated dose of a statin and in many
cases additional lipid-lowering drugs. Patients’ average LDL-C at
baseline was 150 mg/dL. Patients treated with mipomersen 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 average reduction in LDL-C of 28 percent in these high-risk,
difficult-to-treat patients with severe inherited high cholesterol is
very encouraging,” said Evan A. Stein, M.D., Ph.D., Director of the
Metabolic & Atherosclerosis Research Center, Cincinnati, Ohio, and an
investigator on the study. “The nearly 50 mg/dL additional decrease in
LDL-C when added to maximally tolerated statin therapy is above what we
have seen with any other agent in this population, and the side effect
profile of mipomersen continues to be acceptable.”
The trial also met each of its three secondary endpoints with
statistically significant reductions in apo-B, total cholesterol, and
non-HDL-cholesterol. Study results are based on an intent-to-treat
analysis (full analysis set). Data will be submitted for presentation at
a future medical meeting.
“We are excited by these strong data in the second phase 3 trial of
mipomersen,” said Genzyme Chief Medical Officer Richard A. Moscicki,
M.D. “This therapy has the potential to make a major difference in the
lives of patients who are in great need of new treatment options. With
these data, we remain on-track with our development plan for mipomersen.”
There were no new areas of safety concerns identified in the trial. Of
the 83 patients treated with mipomersen, 73 completed the study; nine of
the discontinuations were related to adverse events. Consistent with
previous studies evaluating mipomersen, the most commonly observed
adverse events were injection site reactions and flu-like symptoms.
As in other mipomersen trials, elevations in liver transaminases were
observed that were similar in magnitude and duration to those seen in
other studies. None of these patients had changes in other laboratory
tests to indicate hepatic dysfunction, and there were no Hy’s Law cases.
“Mipomersen has again delivered positive results with this second phase
3 study, and continues to make progress toward the market,” said Stanley
Crooke, Chairman and Chief Executive Officer of Isis Pharmaceuticals.
“Mipomersen represents the power of antisense technology and reflects
our commitment to innovation and technological advancement to create
potent and specific drugs to help people lead healthier and more hopeful
The study was a randomized, double-blind, placebo-controlled trial that
enrolled 124 heFH patients, aged 18 and older with LDL-C levels greater
than 100 mg/dL. Patients were randomized 2:1 to receive a 200 mg dose of
mipomersen or placebo weekly for 26 weeks. The trial was conducted at 26
sites in the United States and Canada.
Late-Stage Development Plan
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). The phase 3 study of mipomersen in hoFH met its primary endpoint
with a 25 percent reduction in LDL-C, and results were presented at the
annual American Heart Association meeting in November. In the first half
of 2011, Genzyme expects to file for U.S. and E.U. approval of the
treatment and to have made progress toward filing in other major
These two filings may also include patients with severe
hypercholesterolemia. A phase 3 study of mipomersen in patients with
severe hypercholesterolemia is fully enrolled with 58 patients and data
are anticipated in mid-2010. The companies have also completed
enrollment in a phase 3 trial involving 158 hypercholesterolemic
patients at high risk for coronary heart disease, and data are
anticipated in mid-2010.
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.
About Familial Hypercholesterolemia
FH is a genetic disorder that results in elevated LDL cholesterol
levels. FH patients are unable to properly metabolize LDL-C due to
dysfunctional LDL receptors, which are responsible for clearing LDL from
plasma. These patients experience a markedly increased risk of premature
cardiovascular disease (CVD) and CVD-related death.
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 so that some LDL receptor
function is preserved. 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 approximately $4.5 billion.
With many established products and services helping patients in
approximately 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, and diagnostic testing. 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 medical need.
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 States.
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 22
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 over 1,600
issued patents worldwide. Additional information about Isis is available
Genzyme Safe Harbor Statement
This press release contains forward-looking statements regarding
Genzyme’s future business plans and strategies including, without
limitation, statements about the presentation of the data from the phase
3 clinical study of mipomersen in patients with heterozygous familial
hypercholesterolemia; the expected timing of the mipomersen development
plan and regulatory filings; and the potential uses and benefits of
mipomersen. 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: the actual timing
of the completion of the analysis of the clinical study results;
Genzyme's ability to accurately understand and predict the outcome and
impact of its clinical studies related to mipomersen; Genzyme’s ability
to continue to support its clinical and other development efforts
related to mipomersen; the actual efficacy and safety of mipomersen; the
outcome of discussions with regulatory authorities regarding clinical
studies of mipomersen; 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-Q for the period ended September 30,
2009. Genzyme cautions investors not to place substantial 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
products. 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, 2008, 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.
Conference Call Information
At 8:30 a.m. Eastern Time today, Isis will conduct a live webcast
conference call to discuss the results of the phase 3 mipomersen study
in heFH patients. Interested parties may listen to the call by dialing
866-831-6272 and refer to passcode “ISIS 2010,” or access the webcast at www.isispharm.com.
A webcast replay will be available for a limited time at the same