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CARLSBAD, Calif. and CAMBRIDGE, Mass., April 25 /PRNewswire/ -- IsisPharmaceuticals, Inc. (Nasdaq: ISIS) and Genzyme Corp. (Nasdaq: GENZ)announced today that the FDA has provided guidance regarding approvalrequirements for mipomersen. The FDA has indicated that reduction ofLDL-cholesterol is an acceptable surrogate endpoint for accelerated approvalof mipomersen for use in patients with homozygous familialhypercholesterolemia (hoFH). The FDA will require data from two ongoingpreclinical studies for carcinogenicity to be included in the hoFH filing,which is now anticipated to take place in 2010. A phase 3 study of mipomersenin hoFH is currently enrolling patients.

The companies plan to conduct an outcome trial to support full approval ofmipomersen for hoFH and to expand its indication to include other patientswith high cholesterol who are at high risk for cardiovascular events. Inresponse to the FDA's guidance, the companies are revising the developmentplan for mipomersen to accelerate plans for an outcome study. Isis andGenzyme plan to communicate further details of the revised development plan asthey are finalized.

'Because our development plan, and our joint plan with Genzyme, has alwaysincluded outcome studies to maximize the profile and commercial potential ofmipomersen, this FDA guidance accelerates these planned studies and simplifiesthe overall development path for mipomersen,' said Dr Stan Crooke, Chairmanand Chief Executive Officer of Isis. 'Conducting an outcome study in parallelwith our continued evaluation of the effects of mipomersen on atherogeniclipids will allow us to submit a much stronger NDA for high risk patients. Weare confident that mipomersen will bring benefit to patients with highcholesterol and remain committed to its development and commercialization.'

'We are pleased that the FDA has given clear direction on what will berequired for the approval of mipomersen, and has acknowledged its potential tohelp high risk patients whose needs are not being met by current therapies,'said Henri A. Termeer, Genzyme's chairman and chief executive officer.'Having outcome data earlier on in the development process will be importantto patients and serve to enhance the value of this treatment. We plan toengage in discussions with regulatory agencies in Europe and the rest of theworld, and look forward to receiving their feedback.'

ABOUT MIPOMERSEN

In early 2008, Isis and Genzyme announced that they had entered into astrategic alliance in which Genzyme will develop and commercialize mipomersen.Final contracts are still being negotiated and are expected to be completedthis quarter.

Mipomersen is a second-generation antisense drug that reduces theproduction of apoB-100, a protein critical to the synthesis and transport of'bad' cholesterol. Cholesterol can be carried in the bloodstream in a varietyof forms, with high-density lipoprotein, or HDL-cholesterol, being the goodform, and low-density lipoproteins, or LDL-cholesterol, and very low-densitylipoproteins, or VLDL-cholesterol, being bad forms directly involved in heartdisease.