The FDA in January rejected the application by Inamed (Santa Barbara, California) to gain clearance for its silicone gel breast implants and, in an associated initiative, raised the bar for gaining such a clearance by Inamed and any other manufacturers of the implants. The agency issued a "not approvable" letter in response to the company's premarket approval application (PMA) for the implants but left the door open for future approval. The FDA asked the company to provide what Inamed termed "additional information" which could lead to further review and ultimate approval. In response to the turn-down, Nick Teti, chairman, chief executive officer and president of Inamed, said, "Although we are disappointed with the current outcome, we appreciate the serious and thorough review of our PMA by the FDA. The letter that we received provides directions for us to follow, and we intend to work cooperatively with the agency to place the PMA in approvable form."

But the requirements outlined by the agency makes the path to clearance significantly steeper. And the non-approvable announcement was followed shortly after by a conference call by senior officials of the FDA's Center for Devices and Radiological Health (CDRH) to issue a new guidance on the implants. The new guidance which revises a document previously revised in February 2003 makes the path to general marketing of silicone breast implants by any company much more rugged. The document requires gathering more data on device safety via more rigorous testing. Specifically, manufacturers will have to supply additional data concerning the modes and causes of rupture. "FDA needs to deal with science that changes over time," said David Feigal, MD, director of CDRH, explaining the agency's impetus for revising its guidance document. "Unlike other countries, the process here is open, and this issue is one where lots of opinion was weighing in at the advisory panel meeting.

"The guidance document is not a regulation but is considered our best advice on how to address an issue at hand," he added. "The issue of silicone-filled breast implants has been under discussion for more than a decade, and we've learned that the fill material, the silicone, is the most important issue that needs to be addressed. Science is a continuous process, and what we've learned is reflected in the new document."

A new section of the guidance document, called "Modes and Causes of Rupture," has been added, replacing a previous section called "Retrieval Study." Feigal said, "Things that predict rupture and bleeding of the silicone outside its shell is the biggest problem with these implants, and much of the discussion at the advisory panel meeting last October was over what was considered an acceptable rupture rate," Feigal said. That panel meeting produced a recommendation to approve the implants but the recommendation suggested less then resounding confidence in the product. The vote was 9-6 for approval, and the head of the panel subsequently sent a letter to the CDRH expressing a variety of concerns about device safety.

About that issue, Feigal said, "What we need to know is whether the rupture rates level off, or if they steadily increase over time, and manufacturers need to use the opportunity to study explanted devices to better understand a rupture and how to make a better product." The document does not specify a timeframe for demonstrating an acceptable level of safety data, he noted. "The timeframe isn't specified, but a minimum time is suggested that we think manufacturers can likely provide evidence of safety and effectiveness. Manufacturers can establish safety and effectiveness using a different timeframe, and that's fine. Data could come from prospective trials or from clinical experience outside the U.S."

The new guidance also is intended to provide a picture of silicone breast implants over time, said Daniel Schultz, MD, director of the Office of Device Evaluation at CDRH. "No device is completely safe. We know there's a failure rate with these implants, but the issue here is that the material could leak outside the fibrous shell. We need to know how often this could happen, when it could happen and why it could happen, and the consequences of all these questions so physicians can manage their patients properly." He added: "A lot of information developed over the last 10 years has increased our assurance over the safety aspects of these products, but additional information is necessary for this product to pass the threshold for approval for marketing." That information could be gathered largely by means of post-approval requirements asked for in the new guidance.

Abbott buys TheraSense in $1.2B stock deal

Abbott Laboratories (Abbott Park, Illinois) and TheraSense (Alameda, California) jointly announced an agreement last month under which Abbott would acquire all of the outstanding stock of TheraSense for $27 a share in cash, the deal valued at about $1.2 billion. TheraSense makes the FreeStyle blood glucose self-monitoring systems, describing itself as a leader "in developing systems that feature a very small sample size, rapid test results and less painful testing." Ed Fiorentino, president of Abbott's MediSense Products (Bedford, Massachusetts) unit, said that the addition of TheraSense enables Abbott to build on its existing success in the blood glucose monitoring business and "allow us to better serve the needs of people with diabetes through advanced technology, a promising pipeline, a broader product line and critical mass in research, development, sales and marketing. In addition, we will provide TheraSense products with a greater international presence and infrastructure through the global reach of our existing MediSense business."

W. Mark Lortz, chairman, president and chief executive officer of TheraSense, said the deal creates an "ideal fit the combination will create significant opportunities in research and development as we progress toward helping people with diabetes through advancements in continuous blood glucose monitoring and future integrated systems." TheraSense entered diabetes testing in mid-2000 with the launch of its FreeStyle blood glucose monitor, a system that has a small sample size requirement (0.3 microliter), 50% to 90% less than most conventional testing systems. This permits finger testing or less painful alternate site testing on the forearm, upper arm, thigh, calf or base of the hand. In October 2003, TheraSense launched its FreeStyle Flash blood glucose monitoring system, which combines the world's smallest glucose meter with a very small sample size, a test time of about seven seconds, a backlit panel display, a lighted test strip port for testing in low light conditions and four customizable daily alarms.

TheraSense recently submitted an FDA premarket approval application for its FreeStyle Navigator Continuous Blood Glucose Monitor, designed to provide real-time glucose data, hypo- and hyperglycemic alarms and trend analysis. FreeStyle Navigator uses TheraSense's patented Wired Enzyme technology and is designed to measure glucose levels in the patient's interstitial fluid every 60 seconds, transmitting the results to a wireless pager-sized receiver worn on a belt or carried in a pocket or purse.

The CozMore Insulin Technology System is being developed by TheraSense in conjunction with Deltec (St. Paul, Minnesota), a provider of infusion systems. Scheduled to be launched in 2Q04, this system combines the TheraSense testing system and insulin delivery options in a small system designed for easier patient self-management.

Abbott entered the blood glucose monitoring field in 1996 with the acquisition of MediSense, the first company to commercialize biosensor technology. Today, MediSense offers other products such as Precision Xtra, the first blood glucose monitor to offer ketone testing, and Precision PCx, a hand-held, point-of-care blood glucose monitoring system used in hospitals.

The acquisition will result in about a 1 cent reduction in earnings per share in 2004 for Abbott and is expected to be accretive thereafter. It is expected to result in one-time charges in the second quarter, primarily for in-process R&D and, throughout 2004, for integration expenses. The transaction, expected to close during 2Q04, is subject to approval by holders of a majority of TheraSense common stock at a special meeting, plus other customary closing conditions.

'Sorting' tech adapted by Exagen Diagnostics

When a physician diagnoses a patient with a life-threatening disease, the information he or she can provide to a patient may have many more uses especially for personalized treatment and ongoing assessment of treatment. Somewhat ironically, a technology developed initially to improve automotive performance is being used by developmental firm Exagen Diagnostics (Albuquerque, New Mexico) to provide this more personalized approach to treatment. Exagen is betting that its use of a "sorting" technology will help patients diagnosed with breast cancer or hepatitis C know just how their disease may progress with the help of its prognostics now in development.

Exagen was founded in 2002 as a spin-off of Quasar International (also Albuquerque), a company focused on automotive applications, not on healthcare. Quasar uses advanced resonance measurement technology and algorithms to sort through large volumes of data to identify defects in millions of automotive parts. Seeing the opportunity for medicine, the founders of Exagen adapted the technology so that it is capable of sorting through large volumes of genomic data. Exagen's platform "has the capability to dramatically accelerate the identification, validation and commercialization of prognostic genomic marker tests," according to the company.

"[Our platform] takes whole genome data, rather than taking a specific subset of genes that are thought to be involved in breast cancer, for example," said Waneta Tuttle, PhD, president and chief executive officer. "It searches the whole genome for markers that correctly classify the condition of interest, for instance, to correctly classify a case of poor prognosis vs. a . . . good prognosis [such as] in the case of breast cancer." She continued: "We have already demonstrated that Exagen's technology can rapidly generate accurate, informative and affordable prognostic aids, signaling the end of 'one-size-fits-all medicine' for serious conditions like breast cancer and hepatitis C."

For hepatitis C alone, the need for a prognostic test is great, since current treatment for the chronic disease can be "debilitating," she told The BBI Newsletter. It is treated with drugs interferon and ribavirin. And the numbers of those with the disease are large. Tuttle said that 4 million people in the U.S. have the disease, which grows to 200 million worldwide.

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