Feb 10 2010
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
placebo.
“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
lives.”
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
international markets.
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.
SOURCE Genzyme Corporation