Alemtuzumab for MS, Mipomersen

In addition to Myozyme, alemtuzumab will be produced at our protein and antibody manufacturing facility in Geel, Belgium. We are in the validation phase of building capabilities for alemtuzumab production-we expect regulatory approval to manufacture both alemtuzumab and Myozyme in 2009.

In the fall of 2007, we presented data from a phase 2 clinical trial of alemtuzumab for multiple sclerosis (MS) to the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis. The results were powerful.

In a three-year comparison between alemtuzumab and Rebif^® (interferon beta-1), patients taking alemtuzumab showed a 73 percent reduction in risk of relapse and at least a 70 percent reduction in risk for progression of clinically significant disability. These remarkable results were achieved with once-per-year dosing for alemtuzumab patients versus three times per week for interferon beta-1. Safety issues were managed-a total of six cases of immune thrombocytopenic purpura (ITP) were diagnosed and treated, with no cases diagnosed in the last 12 months of the study.

We began enrollment at trial sites worldwide in late 2007 for two phase 3 studies to compare the efficacy of alemtuzumab versus Rebif across a two-year period-again measuring alemtuzumab's comparative effect on disability accumulation and relapse rate-one in treatment-naive relapse-remitting MS patients; the other in MS patients who have experienced relapse episodes while on a currently available therapy. The trial will include a comprehensive risk management program for ITP.

Co-developed with Bayer Schering Pharma AG, Germany, alemtuzumab represents a potential blockbuster-sized opportunity to create a whole new standard of care for MS patients in a market that could reach $8-9 billion by the time the therapy would be launched in 2012.

A second powerful therapy will join the Genzyme pipeline with our alliance with Isis Pharmaceuticals: mipomersen, an exciting, novel lipid-lowering therapy currently in phase 3 development. The indication we initially plan to pursue is familial hypercholesterolemia (FH), which creates a greatly increased risk of early coronary events and sudden death. With our launch of Cholestagel in Europe in 2007, we gained valuable insight into the FH market. After appropriate clinical development, the next potential indication pursued for mipomersen will be for other patients with elevated cholesterol at high risk of cardiovascular events.


Early-stage promise Innovation drives sustainable, long-term growth. We are building upon a solid foundation of exciting early-stage programs that will continue to extend our horizon over the next decade and beyond.

In neurology, Genzyme is supporting two early-stage gene therapy programs for Parkinson's disease, including a phase 2 clinical study to develop CERE-120 with our partner Ceregene, Inc., which uses a naturally occurring gene known to protect dopamine-secreting neurons associated with Parkinson's. Other neurology programs include early preclinical research exploring the ventricular system as a means to carry proteins or gene therapies to the central nervous system to treat LSDs, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and muscular dystrophy.

In the cardiovascular area, we're leveraging our gene therapy expertise to target arterial disease. We have made significant advances in the development and potential commercialization of Ad2/HIF-1alpha, an engineered form of the HIF-1alpha gene designed to promote growth of new blood vessels and improve circulation in peripheral arterial disease. We are currently conducting a 300-patient phase 2 clinical trial of Ad2/HIF-1alpha at 40 U.S. and European medical centers, and in 2007 entered into an agreement with Sunway Biotech Co. Ltd. to manufacture, develop and eventually commercialize this promising gene therapy in China.

In immune mediated diseases, Genzyme's early-stage development includes GC1008, our TGF-beta antagonist, for the treatment of idiopathic pulmonary fibrosis (IPF), a potentially fatal lung disease. We completed the phase 1 IPF trial in 2007 and plan to begin a phase 2 study in the second half of 2008. In addition to its oncological applications, GC1008 has the potential to find a broad application as an anti-fibrotic across a wide range of diseases such as renal and liver fibrosis.

With hematologists as a major call point for current Genzyme LSD, oncology and transplant treatments, hematology/oncology is a significant area of expertise to be leveraged in research. We are exploring novel therapies for a range of challenging diseases-including the development of an oral formulation of clofarabine in myelodysplastic syndrome (MDS). We're also in the early stages of studying Mozobil and Thymoglobulin in this same indication, and clofarabine in various leukemias.