Advanced Tissue Sciences Inc. said Monday that statisticalsignificance was reached in a pivotal trial of Dermagraft for diabeticfoot ulcers and the filing of a premarket approval (PMA) applicationis planned for December.

Dermagraft is an engineered human tissue product placed into thewound bed of the diabetic ulcer that's designed to vascularize withunderlying tissue in a few days. It was compared to the standardtreatment of a wet saline solution followed by dry gauze bandaging.

The primary endpoint of the 240-patient study was complete woundclosure at 12 weeks. The La Jolla, Calif., company said a differenceof about 20 percent in favor of Dermagraft was seen in completehealing. Dermagraft patients also healed significantly faster, thecompany said.

The company's stock (NASDAQ:ATIS) was up $2.50 Mondayafternoon at $20 in trading of more than 3 million shares.

Advanced Tissue Sciences (ATS) in April filed a PMA for a similarproduct, Dermagraft-TC, to treat patients with severe burns. An FDAadvisory panel meeting for that product is scheduled for Nov. 19.

While ATS plans to market Dermagraft-TC itself, Dermagraft will besold through a joint venture with Smith & Nephew plc, of London. Ina deal made in April Smith & Nephew paid $10 million up front andwill pay another $5 million upon product approval. Most of the restof the $50 million in potential milestones to ATS are dependent onsales figures. (See BioWorld Today, April 30, 1996, p. 1.)

A product to treat diabetic foot ulcers would be an important one.The condition is characterized by deep, chronic wounds on the feet ofdiabetics. It can lead to amputation.

"The current therapy isn't real successful in healing them and there isalso a high recurrence rate, about 50 percent within a year," saidMarie Burke, director of corporate communications for ATS.

Burke said data on recurrence from the pivotal study may beavailable next April when more complete data are expected to bepresented at the Advanced Wound Care Symposium in New Orleans.

In a small pilot trial about six of 12 Dermagraft patients had woundclosure at 12 weeks vs. one of 12 patients on standard therapy. Therewas no recurrence of ulcers at an average of 14 months in that study.

Burke said the pivotal study was designed to show 20 percent moreDermagraft patients achieved complete healing, a figure that will helpin reimbursement issues. A preliminary economic study showed a 20percent difference in the treatments would justify a Dermagraft priceranging from $3,000 to $5,000 per course of treatment, she said.

About 800,000 diabetic foot ulcers are treated each year in the U.S.,Burke said, and about half of the patients are on Medicare, makingreimbursement a key issue. About $15,000 to $60,000 is spent eachyear on each ulcer that heals, she said.

"The success of the Dermagraft trial represents a significantachievement and confirms our belief that bioengineered human tissuecan provide solutions to important medical problems," said ArthurBenvenuto, chairman and CEO of ATS. "Our efforts with Smith &Nephew are now focused on the submission of a well-prepared PMAapplication to support the FDA in its expedited review of Dermagraft,and in putting our sales and marketing plans into place.

A Smith & Nephew official said a potential launch in the second halfof 1997 is being planned in the U.S. and U.K., with the roll-outcontinuing afterward as quickly as regulatory approvals are received.Smith & Nephew has a large program in tissue repair products andhas sales capabilities in more than 90 countries. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.