Grant for Hunter Syndrome research

Transkaryotic Therapies has received a development grant from the FDA's Office of Orphan Products Development (OOPD) for iduronate-2-sulfatase (I2S), TKT's investigational enzyme replacement therapy for the treatment of Hunter syndrome, also known as MPS II, a rare, fatal disease.

The $300,000 grant will pay for some costs of the company's ongoing pivotal trial. 'We are grateful for this recognition of the importance of our efforts to develop I2S as a potential treatment for Hunter syndrome. We fully support the FDA's mission to encourage clinical development of products for rare diseases and to put agency resources behind these development efforts,' said Michael J. Astrue, president and chief executive officer of TKT.

Since 1989, approximately 36 products supported by OOPD grants have received marketing approval by the FDA. Clinical studies conducted under an Investigational New Drug (IND) application for a rare disease qualify for consideration by the program. Grants of this size are typically awarded to drugs in Phase III clinical trials.

I2S pivotal trial

The I2S pivotal trial, referred to as the AIM (Assessment of I2S in MPS II) study, is a fully enrolled trial designed to evaluate safety and efficacy of weekly and every-other week infusions of I2S administered at a dose of 0.5 mg/kg. Patients will receive a total of fifty-two infusions of either I2S (patients randomized to the weekly dosing regimen), I2S alternating with placebo (patients randomized to the every other week regimen), or placebo. The AIM study is a twelve-month, randomized, double-blind, placebo-controlled trial being conducted at nine sites around the world. The primary efficacy endpoint in the trial is a single composite variable which combines 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/spleen size. TKT expects top-line results from the AIM study in the second quarter of 2005 and, if positive, the company expects to submit applications for marketing approval in both the United States and Europe in the second half of 2005.

About I2S

I2S is a human iduronate-2-sulfatase produced by genetic engineering technology intended for the 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, the only known enzyme replacement therapy in development for the treatment of Hunter syndrome, has been designated an orphan drug in both the United States and Europe. In addition, I2S received Fast Track designation from the FDA in July 2004. A Phase I/II clinical trial in 12 patients was completed in 2002 and all of those patients have remained on I2S as part of an extension study designed to collect long-term safety data.

About Hunter Syndrome

Hunter syndrome is a chromosomally-linked genetic disorder affecting males, also referred to as MPS II. This hereditary disorder is characterized by the body's inability to produce the enzyme iduronate-2-sulfatase, which is essential in the continuous process of replacing and breaking down glycosaminoglycans (GAG). As a result, GAG remains stored in cells in the body causing progressive damage. The symptoms of Hunter syndrome are usually not visible at birth, but usually start to become noticeable after the first year of life. Often the first symptoms may include hernias, frequent ear infections, runny noses, and abnormal facial appearance. As the disease progresses, a variety of symptoms appear including, enlarged liver and spleen, heart failure, obstructive airway disease, sleep apnea, joint stiffness, and, in the severe form, central nervous system involvement. In severe cases, the life expectancy for patients with Hunter syndrome is typically 10-15 years of age. However, in the attenuated form of the disease, patients can survive into the fifth or sixth decade of life.