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.