Transkaryotic Therapies, Inc has dosed the first patient in the Assessment of Iduronate-2-Sulfatase in MPS II (AIM) Pivotal Trial. The AIM study is a randomized, double-blind, placebo-controlled, clinical trial to evaluate the effect of iduronate-2-sulfatase (I2S) over twelve months in patients with Hunter syndrome, also referred to as MPS II. Ninety patients with Hunter syndrome will be enrolled at eight sites around the world. If the results are positive, TKT expects to file applications for market approval in the United States and Europe in 2005. There is currently no effective therapy for Hunter syndrome.

"Patients in the initial trial saw significant improvements in overall activity levels and treatment was generally well-tolerated," said Dr. Joseph Muenzer of the University of North Carolina at Chapel Hill and lead investigator of the study. "We are excited to expand the scope of clinical testing for I2S and are hopeful this study will demonstrate robust clinical benefit in a much wider patient population."

The primary objective of the study is to determine safety and efficacy of I2S as a treatment for Hunter syndrome. Ninety patients will be randomized equally to three treatment groups receiving either weekly or every other week infusions of I2S at a dose of 0.5 mg/kg or weekly infusions of placebo for twelve months. Efficacy outcomes will be measured at baseline and at four month intervals. There will not be an interim analysis performed in the study. The primary efficacy endpoint will be a single composite variable. The composite variable will combine two clinical measurements: forced vital capacity as a measure of respiratory function and the six-minute walk test as a measure of functional capacity. Additional efficacy endpoints include measurements of joint range of motion and combined liver and spleen size.

TKT previously conducted a Phase I/II randomized, double-blind, placebo-controlled clinical trial to evaluate the safety of I2S and its clinical activity in twelve patients affected with Hunter syndrome. Three doses were studied and within each dose group three patients were randomized to receive I2S and one patient to receive placebo bi-weekly for six months. Results of the study showed that I2S was generally well-tolerated and demonstrated evidence of clinical activity in several critical aspects of the disease, including respiratory function and functional capacity.

Data from the six month Phase I/II study was presentedin October 2002.

I2S is a human iduronate-2-sulfatase produced by genetic engineering technology intended for long-term treatment of Hunter syndrome. The rationale for the therapy is that I2S would replace enzyme that is deficient in patients with Hunter syndrome and either stop or reverse disease progression. I2S has been designated an orphan drug in both the United States and Europe and is the only known enzyme replacement therapy in development for the treatment of Hunter syndrome.

- Bio.com