By Mary Welch
Four months after the FDA shocked Advanced Tissue Sciences Inc. (ATS) with a "non-approvable" letter for Dermagraft, the company has won a treatment investigational device exemption (IDE) from the agency to use the wound healing aid for diabetic foot ulcers.
Jack Strube, executive director of finance for La Jolla, Calif.-based ATS, said the list of firms granted a treatment IDE is not long, and ATS may even be the first. "Let's just say there's not a long roll call," he said.
The treatment IDE is a new regulatory provision for devices that allows promising products to be made available to patients with serious diseases for which there is no satisfactory treatment, while the product is still in clinical trials.
Unlike the customary IDE, a treatment IDE allows for unlimited centers at which to recruit an unlimited number of patients, and provides for reimbursement for the product.
ATS and its partner, London-based Smith & Nephew plc, will now contact a small number of centers and hospitals across the country, asking each center's investigational review board to join the treatment IDE program so qualifying patients may obtain Dermagraft.
The hospitals are required to report six-month patient results and file an annual report with the FDA concerning patient progress. Those results will not be included in the Phase III outcomes for several reasons, including lack of a control group as well as protocol variations.
Pricing Yet To Be Determined
Pricing while the product is under the treatment IDE has not yet been determined, but the FDA allows for the company to recover the costs of manufacturing and distributing the product. ATS is now working with the Health Care Financing Administration (HCFA) and other payers to address the reimbursement issue.
Dermagraft is a bioengineered, living, metabolically active skin implant derived from discarded human foreskin tissue. The product consists of viable dermal fibroblasts cultured on a bioabsorbable scaffold that secretes vital matrix proteins, growth factors and glycosaminoglycans (a protein-polysaccharide complex needed for wound healing to occur). (See BioWorld Today, June 15, 1998, p. 1.)
Already available in Canada, the U.K., Ireland and Finland, Dermagraft is cryopreserved and delivered frozen to the treating physician, who thaws and implants it into diabetic foot ulcers, where it is designed to vascularize with underlying tissue after a few days. Diabetic foot ulcers are responsible for up to 85 percent of the 60,000 foot and leg amputations that take place annually in the U.S.
When the FDA advised ATS to file for a treatment IDE, it also recommended the company perform another randomized, multicenter clinical study. The FDA's General and Plastic Surgery Devices Advisory Committee in January recommended approval of Dermagraft, with the stipulations of a post-marketing study and extensive physician training, but the regulatory agency opted not to follow that advice.
In mid-June, the FDA stated that while "Dermagraft shows promise for the effective treatment of diabetic foot ulcers," it didn't believe that the company's reliance on retrospective analysis of the product's pivotal trial was adequate.
"The FDA decided that it took another clinical trial to clear up what they saw as a problem with the retrospective analysis," said Strube. "At that time, we thought it set the program back two years. But we have gotten a protocol understanding with the FDA, and we have also been successful in working out an interim analysis agreement. Depending on how the data goes, any launch — assuming FDA approval, of course — would be six months to 18 months later than we planned before the non-approvable letter."
Market Approval And Launch Possible By Mid-1999
The 30-center study, which started in late August, calls for a total enrollment of 330 patients for 12 weeks. But, under the interim analysis program, the company can submit data on 180 patients (90 getting Dermagraft and 90 in the control group).
If the interim study shows a statistically significant recovery rate, the company may file for pre-market approval (PMA) and potentially reach the market by mid-1999.
If results are not favorable, the company must enroll the entire 330 patients, which Strube says would stretch any marketing launch until early 2000. He said the time required to enroll 180 patients is uncertain.
ATS also expects to begin a pilot study of Dermagraft for venous ulcers before year's end. The company's stock (NASDAQ:ATIS) closed Monday at $3, unchanged. *