West Coast Editor

In a development that must have pleased owner-to-be Shire Pharmaceuticals Group plc as well as investors, Transkaryotic Therapies Inc. reported positive top-line data from its pivotal Phase III trial with iduronate-2-sulfatase (I2S) for Hunter syndrome, and the company expects to file for approval in the U.S. and Europe in the fourth quarter.

TKT's stock (NASDAQ:TKTX) closed Monday at $36.60, up $2.35.

Specifically, patients in the study who were given 0.5 mg/kg of I2S weekly showed a statistically significant improvement in the primary efficacy endpoint (p=0.0049) compared to those who got placebo - and the news may get even better.

"This is a very large and very involved trial," David Pendergast, Cambridge, Mass.-based TKT's president and CEO, said in a conference call. Not only did the primary endpoint pan out, "but there's a lot of understanding about the impact of this enzyme on the disease" that is still in the data set and yet to be analyzed.

In the study called AIM, which stands for "Assessment of I2S in MPS II," the primary efficacy endpoint was a composite endpoint of forced vital capacity and six-minute walk test, which are clinical measures previously used to assess clinical benefit. MPS II is another name for Hunter syndrome, a rare, life-threatening genetic disorder.

Specifically, the mean improvement from baseline to week 53 in predicted forced vital capacity was 3.4 percent in patients who got I2S, compared to 0.8 percent in those who got placebo. The mean increase from baseline to week 53 in the distance walked by patients receiving I2S was 44 meters as compared to 7 meters in the placebo group.

The AIM study was a Phase III double-blind, placebo-controlled trial conducted at nine sites around the world, including the U.S., the UK, Germany and Brazil. Enrolled were 96 patients with Hunter syndrome, randomized to one of three groups with each patient receiving a total of 52 infusions of either I2S, I2S alternating weekly with placebo, or placebo.

Ninety-four patients completed the study, and all chose to take part in an open-label extension study of I2S at the 0.5-mg/kg weekly dose. I2S has been designated an orphan drug in the U.S. and the European Union, and no effective therapy exists for the enzyme-shortage disorder.

The trial also evaluated 0.5 mg/kg of I2S every other week compared to placebo and reached statistical significance, but "at the end of AIM trial, we switched folks over to the weekly dose because that was the primary comparison dose," Pendergast said.

"All patients in the extension trial are on the weekly dose, and they will remain on the weekly dose until we complete our analysis and determine what we believe to be the commercial dose and agree to that with the regulatory authorities," he added.

The potential market for Hunter syndrome remains somewhat unclear.

"We have active programs in terms of identifying and looking for these patients but at this point in time we're not giving updates on the number of patients we have identified," Pendergast said, but the company believes about 2,000 patients worldwide are eligible for reimbursement and might be treated with the enzyme replacement.

This spring, Basingstoke, UK-based Shire disclosed its plan to take over TKT, paying $37 in cash for each share of TKT common stock in a deal estimated at $1.6 billion. That deal is expected to close in the third quarter, with FDA approval of I2S possible in the fourth quarter, and launch of the product in 2006. (See BioWorld Today, April 22, 2005.)