TKT reports positive results for Hunter Syndrome and Shire

Positive results have been seen in Transkaryotic Therapies' (TKT) pivotal Phase III clinical trial evaluating its investigational human enzyme replacement therapy, iduronate-2-sulfatase (I2S), for the treatment of patients with Hunter syndrome.

Hunter syndrome, also known as MPS II, is a rare, life-threatening genetic disorder with no available treatment. In the trial, patients who received 0.5 mg/kg of I2S on a weekly basis showed a statistically significant improvement in the primary efficacy endpoint (p=0.0049) compared to patients receiving placebo. Based on these results, TKT expects to file for regulatory approval of I2S in both the United States and Europe in the fourth quarter of 2005.

Shire Pharmaceuticals announced in April 2005 that it had signed a definitive agreement to acquire TKT and, subject to approval by the shareholders and the regulators, the transaction is expected to close in the summer of 2005. Its chief executive, Matthew Emmens commented: 'We are very pleased that the announcement of the AIM study results from TKT are positive and that they plan to file the product license applications in the US and Europe as targeted, in the fourth quarter of 2005. Enzyme Replacement Therapy (ERT) product development is lower risk than other new chemical entities. This lower risk profile is one of the reasons why TKT is such an attractive fit for Shire.

'Patients with Hunter syndrome are now one step nearer to being able to obtain treatment for this debilitating and life threatening condition with the release of this new trial data from TKT.'

The primary efficacy endpoint of the trial, also referred to as the AIM study ("Assessment of I2S in MPS II") was a composite endpoint of two clinical measures previously used to assess clinical benefit in MPS disorders - forced vital capacity and six-minute walk test. The mean improvement from baseline to week 53 in percent predicted forced vital capacity was 3.4% in patients receiving I2S compared with 0.8% in patients receiving placebo. The mean increase from baseline to week 53 in the distance walked by patients receiving I2S was 44 metres as compared with seven metres in the placebo group.

Dr Joseph Muenzer, of the University of North Carolina at Chapel Hill, an internationally recognised leader in the diagnosis and treatment of MPS disorders and the lead investigator of the AIM study said: 'These findings are very encouraging for the medical and patient communities as we believe ERT can bring new hope for patients and families addressing many of the symptoms associated with Hunter syndrome.'

Treatment with I2S was generally well-tolerated by patients in the trial. The most common adverse events observed were associated with the clinical manifestations of Hunter syndrome. Of the adverse events considered possibly related to I2S, infusion related reactions were the most common and were generally mild. No patient withdrew from the trial due to an adverse event considered related to I2S.

'We are extremely excited about the outcome of the study. In addition, we are very thankful to all the patients and their families who participated in this one year trial. Their commitment to this programme was instrumental in generating the data which we believe will support regulatory approval of I2S,' said Dr Kip Martha, senior vice president and cmo of TKT.

About I2S and Hunter Syndrome

I2S is a human iduronate-2-sulfatase produced by genetic engineering technology intended for long-term treatment of Hunter syndrome. TKT's I2S replaces an enzyme that is deficient in patients with Hunter syndrome, and therefore could potentially either stop or ameliorate the clinical manifestations of the disease. TKT's I2S product has been designated an orphan drug in both the United States and the European Union. There is currently no effective therapy for Hunter syndrome. Hunter syndrome is a hereditary disorder 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, decreased endurance, obstructive and restrictive airway disease, sleep apnea, joint stiffness, and, in some cases, central nervous system involvement. If central nervous system involvement exists, the life expectancy for patients with Hunter syndrome is typically 10-15 years of age, however, some patients can survive into the fifth or sixth decade of life. TKT believes there are approximately 2,000 patients worldwide afflicted with Hunter syndrome in countries where reimbursement may be possible.