SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities and Exchange Act of 1934
JUNE 11, 1998
Date of Report
(Date of earliest event reported)
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ADVANCED TISSUE SCIENCES, INC.
(Exact name of registrant as specified in its charter)
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Delaware 0-016607 14-1701513
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(State or other jurisdiction (Commission (I.R.S. Employer
of incorporation or organization) File No.) Identification No.)
10933 North Torrey Pines Road, La Jolla, California 92037
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(Address of principal executive offices) (Zip Code)
Registrant's telephone number, including area code: (619) 450-5730
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Item 5. Other Events
On June 11, 1998, Advanced Tissue Sciences, Inc. (the "Company") issued a
press release reporting that the U.S. Food and Drug Administration (FDA) had
requested an additional controlled clinical trial be completed in support of
its Premarket Approval (PMA) application of Dermagraft(R) in the treatment of
diabetic foot ulcers. As had been previous reported, the Company stated that
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. The FDA indicated the PMA
application was not approvable without supportive data from the additional
clinical trial. The Company also reported the FDA had 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.
Separately, the Company reported it requested a re-inspection of its
manufacturing facility and that the FDA has scheduled the re-inspection for
August 1998.
The press release is attached hereto as Exhibit 28.
Item 7. Exhibits
Exhibit
Number Description
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28 Press Release of the Company dated June 11, 1998
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
ADVANCED TISSUE SCIENCES, INC.
Date: June 17, 1998 By: /s/ Arthur J. Benvenuto
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Arthur J. Benvenuto
Chairman and Chief Executive
Officer
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EXHIBIT INDEX
Exhibit
Number Description Page
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28 Press Release of the Company dated June 11, 1998
Exhibit 28
FOR INFORMATION CONTACT:
Arthur J. Benvenuto Gail K. Naughton, Ph.D.
Chairman and Chief Executive Officer President and Chief Operating Officer
619/450-5735 619/450-5731
Jack D. Strube Gary D. Gentzkow, M.D.
Executive Director, Finance Executive Director, Worldwide Medical Affairs
619/450-5802 619/450-5836
FOR IMMEDIATE RELEASE
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FDA RESPONDS TO PREMARKET APPROVAL APPLICATION
La Jolla, CA, June 11, 1998 - 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."
<PAGE>
"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.
<PAGE>
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.
