Genzyme's sustainability depends upon constant innovation and discipline in the drug discovery and development process. We take a portfolio approach, focusing development efforts on specific medical areas and selecting from a broad technology base to identify the best treatment alternative for a particular disease.

Myozyme: our largest development program
Myozyme, for Pompe disease, is our fourth lysosomal storage disorder therapy. In late 2004, we filed for approval in Europe and plan to do the same in the United States and Japan in 2005. We anticipate decisions from U.S. and European agencies in early 2006. We are putting such great emphasis on Myozyme because there is no approved treatment for Pompe disease, which in its infantile-onset form kills the majority of patients before they reach age 1. Newborn screening is also central to Myozyme's success, since we believe that patients with the most severe form of the disease will receive the greatest benefit if they are treated before 6 months of age.

Tolevamer: a new polymer application
Based on the positive results of a multicenter phase 2 clinical trial of tolevamer sodium, in early 2005 Genzyme began enrolling patients in a phase 3 trial involving approximately 1,000 patients and more than 250 clinical centers in Europe, North America, and Australia. Tolevamer is being developed as a novel, nonabsorbed polymer therapy that could be the first nonantibiotic treatment for Clostridium difficile-associated diarrhea (CDAD).

CDAD is a widespread problem among hospitalized patients, with more than 400,000 cases annually in the United States alone, resulting in prolonged hospitalization and approximately 5,000 deaths. As a nonabsorbed binder of the toxins that cause CDAD, Tolevamer offers the potential to reduce antibiotic use as well as to treat the disease effectively. The data indicate that it may be particularly valuable in preventing recurrence and consequent rehospitalization.

TSH: beyond Thyrogen
Well established as a diagnostic that has changed thyroid cancer management, Thyrogen, our thyroid-stimulating hormone (TSH) product, is now progressing toward therapeutic use in remnant ablation following the surgical removal of the cancerous thyroid. We received approval for this indication in Europe in early 2005 and expect FDA action in the second half of the year.

In early 2005, we completed our phase 1 clinical trial of TSH in nontoxic multinodular goiter. There is currently no completely effective treatment for this condition, and our approach offers the potential of efficacy by noninvasive means. We are now developing a formulation of recombinant TSH best suited to the goiter patient population. Looking ahead, we are investigating the potential of TSH in other diseases with different patient populations, including osteoporosis and other bone disorders.