Genzyme Corp. (NASDAQ: GENZ) and Isis Pharmaceuticals Inc.
(NASDAQ: ISIS) today announced results of two phase 3 studies of
mipomersen in patients who had high cholesterol levels while on
maximally tolerated lipid-lowering therapy. In the study of
patients with severe hypercholesterolemia, mipomersen reduced
LDL-C, the primary endpoint, by 36 percent compared with a 13
percent increase for placebo. In the study of patients with high
cholesterol at high cardiovascular risk, mipomersen reduced LDL-C
by 37 percent compared with a 5 percent reduction for placebo. Both
studies met all of their secondary endpoints. Frequently observed
adverse events were injection site reactions, flu-like symptoms and
elevations in liver transaminases, as seen in previous studies.
With these studies, the companies have completed the four phase
3 studies that are planned to be included in the initial U.S. and
E.U. regulatory filings for mipomersen. These filings, expected in
the first half of 2011, will seek approval for the treatment of
patients with homozygous familial hypercholesterolemia (FH), and
may also include patients with severe hypercholesterolemia. The two
previous phase 3 studies of mipomersen, which focused on patients
with homozygous and heterozygous FH, also met their primary and
secondary endpoints.
“We are pleased with the robust efficacy of mipomersen across
all four phase 3 trials. These data, along with the emerging safety
profile, support our focused approach on patients at highest
cardiovascular risk who are in the greatest need of new
treatments,” said Genzyme Senior Vice President John Butler. “With
completion of these studies, we remain on-track with our plans for
mipomersen.”
Phase 3 Study in Patients with
Severe Hypercholesterolemia
This double-blind, placebo-controlled trial included 58 patients
with severe hypercholesterolemia who were already taking maximally
tolerated lipid-lowering medications. Severe hypercholesterolemia
patients were defined as those who have LDL-C levels ≥ 200 mg/dL
with baseline cardiovascular disease (CVD) or LDL-C levels ≥ 300
mg/dL without CVD. Patients were randomized 2:1 to receive a 200 mg
dose 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. The trial
also met each of its three secondary endpoints with statistically
significant reductions in apo-B, non-HDL-cholesterol and total
cholesterol. Study results are based on an intent-to-treat analysis
(full analysis set). Detailed results will be submitted for
presentation at a medical meeting.
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.
There was one death in the study due to acute coronary syndrome in
a patient treated with mipomersen that was reported as unrelated to
treatment.
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 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.
“There are patients, such as those with familial
hypercholesterolemia, who are on maximally tolerated doses of
currently available medications and still are very far from
appropriate target goals,” said James A. Underberg, M.D., of the
New York University Center for Cardiovascular Disease Prevention.
“For these high risk patients, there exists a tremendous need for
additional lipid lowering therapies.”
Phase 3 Study in
Hypercholesterolemic Patients at High Risk of Developing Coronary
Heart Disease
This double-blind, placebo-controlled trial included 158
patients with hypercholesterolemia (LDL-C ≥ 100 mg/dL) and at high
risk of developing coronary heart disease (CHD) who were taking a
maximally tolerated dose of a statin. Patients were randomized 2:1
to receive a 200 mg dose of mipomersen or placebo weekly for 26
weeks. This study was conducted at 43 sites in the United States
and Canada. This was the first study of mipomersen designed to
evaluate patients with diabetes. More than 50 percent of patients
in the study had type 2 diabetes.
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. The trial also met
each of its three secondary endpoints with statistically
significant reductions in apo-B, non-HDL-cholesterol and total
cholesterol. Study results are based on an intent-to-treat analysis
(full analysis set). Detailed results will be submitted for
presentation at a medical meeting.
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. There was one death in the study due to
acute myocardial infarction in a patient treated with placebo.
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. In many cases, these elevations were associated with
increased hepatic fat content, as measured by MRI. No patients had
changes in laboratory tests indicative of clinically significant
hepatic dysfunction, and there were no Hy’s Law cases.
“The completion of these phase 3 studies is a significant
milestone for the mipomersen program, for antisense technology and
for patients in need,” said Isis Pharmaceuticals Chairman and CEO
Stanley T. Crooke. “Mipomersen’s lipid-lowering activity
demonstrates the value antisense drugs can bring to patients. Our
robust pipeline is evidence of the efficiency of our technology and
the potential value we can create.”
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 the genetic disease homozygous FH (hoFH). These
initial filings may also include patients with severe
hypercholesterolemia. 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.
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 in February reported that the
phase 3 study of mipomersen in heFH met its primary endpoint with a
28 percent LDL-C reduction, and data will be presented at the
European Society of Cardiology meeting this month. In addition,
studies are ongoing and planned to evaluate alternative dosing
regimens.
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.
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 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 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.
About Isis
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,
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; 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/A for the period ended March 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.
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.
Conference Call
Information
Genzyme and Isis will host a conference call today at 8:30 a.m.
Eastern. To participate in the call, please dial 1-517-308-9370 and
refer to pass code “Genzyme.” This call will also be webcast live
on the investor events section of www.genzyme.com and on
www.isispharm.com. A replay of this call will be available by
dialing 1-203-369-0784. Replays of the call and the webcast will be
available until midnight on August 12, 2010.
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