Genzyme Corp and Isis Pharmaceuticals Inc announced that the phase III study of mipomersen in patients with homozygous familial hypercholesterolemia (hoFH) met its primary endpoint, with a 25 per cent reduction in LDL cholesterol after 26 weeks of treatment, vs. 3 per cent for placebo (p<0.001). This study also met each of its three secondary endpoints of reduction in apolipoprotein B, total cholesterol and non-HDL cholesterol (all p<0.001).

Although the patients were on maximally tolerated statins and other lipid-lowering therapies, their average LDL-C at baseline was greater than 400 mg/dL. The reductions observed in the study were in addition to those achieved with the patients' existing therapeutic regimen. Full data from the study will be presented at a future medical meeting.

"These are promising results for a very high-risk patient population that is in great need of new treatment options," said Genzyme chief medical officer Richard A Moscicki. "This is one of the largest studies of hoFH patients ever conducted, and we are very encouraged by these robust data and the emerging profile of the drug. With these results, we remain on-track with our development plan for mipomersen."

Consistent with previous studies evaluating mipomersen, the most commonly observed adverse events were injection site reactions, flu-like symptoms and elevations in liver transaminases. Of the 34 patients treated with mipomersen, 28 completed the study. One patient discontinued due to elevations in liver transaminases.

"The results announced today are good news for patients with hoFH," said John J P Kastelein, professor of Medicine and chairman of the Department of Vascular Medicine at the Academic Medical Centre Amsterdam. "The currently available treatments do not provide the magnitude of lipid lowering that these patients need, leaving them at extraordinarily high risk of cardiovascular events. Mipomersen has the potential to change the standard of care for hoFH patients, whose life expectancies are limited due to the severity of this disease."

"This is a historic moment for Isis and antisense technology as this study represents the first successful phase 3 trial with a systemically delivered antisense drug," said Isis Pharmaceuticals chairman and CEO Stanley T Crooke. "This drug exemplifies the potential of the antisense drug discovery platform pioneered by Isis. We look forward to benefitting patients in need with mipomersen and other drugs in our pipeline."

The trial was a randomized, double-blind, placebo-controlled study that enrolled 51 hoFH patients, aged 12 and older. Seven patients were aged 12 to 17. Patients were randomized 2:1 to receive a 200 mg dose of mipomersen or placebo via weekly injections for 26 weeks. The trial was conducted at 10 sites in seven countries in North America, Europe, Asia, South America and Africa.

Data from this phase-3 study of mipomersen in patients with hoFH will form the basis of Genzyme's initial regulatory filing for marketing approval, which is anticipated in the second half of 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 lipoproteins.

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.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners.