LA JOLLA, Calif., June 11 /PRNewswire/ -- Advanced Tissue Sciences, Inc.
(Nasdaq: ATIS) and its joint venture partner, Smith & Nephew plc, announced
today that the U.S. Food and Drug Administration (FDA) has requested an
additional controlled clinical trial be completed in support of their
Premarket Approval (PMA) application of Dermagraft(R) in the treatment of
diabetic foot ulcers. The design of the trial, including the number of
patients to be enrolled, is currently under discussion with the FDA. Subject
to the outcome of these discussions, the Company believes the additional data
required by the FDA could be available approximately twelve to twenty-four
months after trial initiation, assuming a reasonable rate of patient
enrollment and data consistent with the previous PMA submission. Separately,
the FDA also suggested that a Treatment Investigational Device Exemption (IDE)
be submitted. The Treatment IDE is a new regulatory provision for devices
that permits companies to make available promising new products under an
agreed clinical protocol to patients with serious diseases for which there is
no satisfactory alternative.
In January 1998, an FDA advisory panel recommended approval of Dermagraft
in the United States with the condition that Advanced Tissue Sciences perform
a post-marketing study to confirm efficacy and provide physician training.
However, since the panel meeting, the FDA continued to raise concerns about
basing approval on a retrospective analysis on a subset of the data together
with a post-marketing study to confirm efficacy, and has indicated the PMA
application is not approvable without supportive data from the additional
clinical trial.
The FDA indicated that it had considered their advisory panel's
recommendation. However, the FDA believes the additional data are needed
prior to approval, rather than post-approval as had been recommended by the
advisory panel. Specifically, the FDA stated, "The data you have provided
demonstrate that Dermagraft shows promise for the effective treatment of
diabetic foot ulcer patients. This potential benefit was further reinforced
with your analysis of (the) narrow range MTT Dermagraft patients. However, to
place your PMA in approvable form, FDA believes that data from a prospective,
randomized concurrently-controlled, multi-center clinical study is necessary
to evaluate the safety and effectiveness of the narrow MTT range Dermagraft."
"We are obviously disappointed the FDA elected not to follow their
advisory panel's recommendation for conditional approval. While we strongly
believe the existing data support the safety and effectiveness of Dermagraft,
we are now moving forward aggressively to provide the additional data
requested by the FDA," said Arthur J. Benvenuto, Chairman and Chief Executive
Officer of Advanced Tissue Sciences. "We do, however, appreciate the FDA's
proposal to consider making Dermagraft available to patients prior to approval
under a Treatment IDE. This approach should provide an opportunity for
leading physicians and patients in need to have access to this exciting new
treatment alternative."
In referring to the proposed Treatment IDE the FDA noted, "Because your
data have shown the promise of your device in the narrow biologically active
MTT range, we believe that a treatment IDE for patients may also be
appropriate and furthermore suggest you pursue approval of such an IDE at the
same time you are gathering prospective data in support of your narrow MTT
range product in a separate clinical trial."
The PMA application was based on the results from a subset of the patients
in a controlled pivotal clinical trial receiving Dermagraft within a
therapeutic range identified retrospectively from the clinical trial. In the
trial, each of the Dermagraft-treated patients received one piece of
Dermagraft weekly for up to eight weeks. The primary endpoint was complete
wound closure at twelve weeks. At twelve weeks, 50.8% (31 of 61) of the
evaluable Dermagraft patients receiving product within the identified
therapeutic range achieved complete healing as compared to 31.7% (40 of 126)
of the evaluable patients treated with conventional therapy. Data from a
supplemental clinical trial that did not include a control group, using
Dermagraft within the therapeutic range, was consistent with the controlled
pivotal trial with 51.3% (20 of 39) of the evaluable Dermagraft patients
achieving complete healing at twelve weeks.
"Although this decision will mean a delay before the U.S. launch, our
growing experience with Dermagraft confirms our confidence in this ground
breaking technology," said Chris O'Donnell, Chief Executive of Smith & Nephew.
"Dermagraft has been commercialized in a number of countries, including Canada
and the United Kingdom, achieving an enthusiastic response from clinicians and
excellent healing results with patients from an increasing number of clinics."
Advanced Tissue Sciences and Smith & Nephew are pursuing the worldwide
commercialization of Dermagraft through a fifty-fifty joint venture formed in
April 1996. The joint venture was expanded in January 1998 to include the
worldwide development and marketing of Dermagraft and Dermagraft-TC(R), and
future product developments, for venous and pressure ulcers, burns and other
skin wounds. Under the joint venture agreement, Advanced Tissue Sciences has
principal responsibility for manufacturing and Smith & Nephew has primary
responsibility for the worldwide sales and marketing of the joint venture's
products. Clinical trials of Dermagraft in the treatment of venous and
pressure ulcers are currently being designed by the joint venture.
Separately, Advanced Tissue Sciences reported it requested a re-inspection
of its manufacturing facility. The FDA has advised the Company that it has
scheduled the re-inspection for August 1998. As previously announced, the
Company has continued to manufacture and, based on product availability, ship
and distribute both Dermagraft and Dermagraft-TC, where approved.
The matters discussed in this press release involve risks and
uncertainties. In particular, the Company will need to successfully complete
an additional controlled clinical trial of Dermagraft in the treatment of
diabetic foot ulcers and submit a revised premarket approval application to
the FDA. No assurance can be given that the FDA will approve the additional
clinical trial as designed, the Company will successfully complete the
clinical trial, the clinical trial will be completed within any specific
timeframe or the Company will obtain FDA or other regulatory approvals of
Dermagraft (or that any such approvals will be obtained on a timely basis).
In addition, there can be no assurance the Company can successfully scale up
manufacturing processes, launch its products within reasonable timeframes,
obtain reimbursement for, or successfully commercialize any such product.
Comments in regard to the Company's manufacturing facility relate to an
inspection by the FDA in March 1998 in which the FDA notified the Company of
numerous objectionable observations with respect to its manufacturing and
quality assurance processes and systems. The Company responded to the issues
raised by the FDA and the manufacturing facility is scheduled to be re-
inspected by the FDA. There can be no assurance, however, that the Company
will be able to satisfy the FDA's concerns, that the FDA will not raise
additional issues on re-inspection, or that other actions will not be taken
with respect to the Company's manufacturing and quality assurance processes
and systems. These and other risks are detailed in the Company's publicly
available filings with the Securities and Exchange Commission including the
Company's Annual Report on Form 10-K for the year ended December 31, 1997.
Actual results may differ materially from those currently anticipated as a
result of such risks.
SOURCE Advanced Tissue Sciences, Inc.
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Company News On-Call: http://www.prnewswire.com or
fax, 800-758-5804, ext. 532975
CONTACT:
Arthur J. Benvenuto Chairman and Chief
Executive Officer, 619-450-5735, Jack D. Strube, Executive
Director, Finance, 619-450-5802, Gail K. Naughton, Ph.D.,
President and Chief Operating Officer, 619-450-5731, or Gary D.
Gentzkow, M.D., Executive Director, Worldwide Medical Affairs,
619-450-5836, all of Advanced Tissue Sciences
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