TKT Hopes To Break Even In 2006 Following Hunter Syndrome Therapy BLA

Transkaryotic Therapies expects its Phase III Hunter syndrome therapy to help the company "break even" by late 2006.

By refocusing on "what we've historically done best" - enzyme replacement therapy for lysosomal storage diseases - "we put a real heavy emphasis on having the lowest-risk possible way to try to be profitable by sometime in late 2006," CEO Michael Astrue said Feb. 24 at a Biotechnology Industry Organization investor conference in New York.

Following the outlicensing of TKT's gene activation and gene therapy platforms, the two key movers toward profitability will be iduronate-2-sulfatase (I2S) for Hunter syndrome, slated for BLA and MAA filing in 2005, and market expansion for the ex-U.S. Fabry disease treatment Replagal (agalsidase alfa), Astrue said. TKT reported a net loss of $1.75 per share in the first nine months of 2003.

Astrue referred to I2S as the "crown jewel" of TKT's pipeline, and touted the Phase III AIM trial as "the largest study in the history of lysosomal storage diseases."

TKT is enrolling 90 patients at nine sites on three continents at an estimated cost of $15 mil. Enrollment is expected to close in early March; results are anticipated in the second quarter of 2005. "We believe that the data is positive and that this study will be adequate for approval," Astrue declared.

The biologic has orphan status in both the U.S. and Europe. There are an estimated 2,000 patients diagnosed with Hunter syndrome (also known as mucopolysaccharidosis II, or MPS-II,) worldwide.

TKT's development program for I2S reflects lessons learned from the approval of Biomarin/Genzyme's MPS-I (Hurler-Scheie syndrome) therapy Aldurazyme (laronidase), Astrue noted (¹ (Also see "Genzyme Aldurazyme Patient Registry Will Evaluate AEs, Antibody Formation" - Pink Sheet, 5 May, 2003.), p. 23).

"We've watched the clinical trials for Aldurazyme and the launch of Aldurazyme as carefully as we can" and "that has influenced the clinical and regulatory path" of I2S, he said. "I think in the past we perhaps didn't give enough thought to endpoints and entry criteria in our trials."

Replagal may be one case in point: an FDA advisory committee recommended against approval of the agent due to doubts about the appropriateness of the surrogate endpoint used in pivotal trials (² (Also see "TKT Replagal Surrogate Data Should Be Reworked For Accelerated Approval" - Pink Sheet, 20 Jan, 2003.), p. 14). The committee instead favored Genzyme's competing therapy Fabrazyme (agalsidase beta), which was approved with orphan exclusivity in April 2003 (³ (Also see "Fabrazyme Approved; FDA Weighing What Confirmatory Data Will Be Needed" - Pink Sheet, 28 Apr, 2003.), p. 3).

TKT withdrew its Replagal BLA in January after FDA determined that a head-to-head trial versus Fabrazyme would be a prerequisite for approval (⁴ 'The Pink Sheet' Jan. 19, 2004, In Brief). The two agents share orphan exclusivity in Europe.

The I2S pivotal trial is using a composite endpoint of forced vital capacity and a six-minute walk test, "the exact same endpoints...[FDA's] advisory committee blessed in the approval of Aldurazyme," Astrue noted.

Astrue pointed out that "there is no known competition" in drug development for Hunter syndrome. "We've acquired what we believe is all the relevant intellectual property, we own the gene," he maintained. TKT licensed the gene from Women's and Children's Hospital in Adelaide, Australia.

In the near-term and going into 2005, TKT will continue to rely on Replagal, its only marketed product, for revenue, Astrue said. The agent was approved in Canada in the first quarter, is approved in Australia and is pending in Japan; launches in Canada and Australia are slated for the second half of 2004.

Canadian sales are projected to make a "significant contribution to our bottom line in 2005," Astrue said. He predicted that Replagal will be a $100 mil. product in 2006.

TKT expects a boost in European sales of Replagal following the looming $55 mil.-$65 mil. buyout of TKT's European subsidiary. The deal will allow TKT "the ability to make some long-term decisions, which I don't currently have the option to do," Astrue said.

The company's other agent in active development, Gaucher disease gene therapy glucocerebrosidase, is targeted for outlicensing. GCB is expected to enter clinicals in the second quarter.