A CDU

The cytokine interleukin-6 plays an important role in triggering the rapid damage to heart muscle function that can develop in people with septic shock following infection with meningococci, a condition that often is fatal. The team making that discovery says it will be important to investigate IL-6 as a target for therapeutic agents. Simon Nadel, consultant in pediatric intensive care at St. Mary's Hospital (London), told The BBI Newsletter's sister publication, BioWorld International. "One of the key questions now is whether it will be possible to develop new treatments either to suppress the production of interleukin 6, or neutralize it."

Nazima Pathan and colleagues reported their work in a paper in The Lancet. Pathan, a clinical research fellow at Imperial College (also London), said: "We were able to rapidly screen the pro-inflammatory response to sepsis on a genome-wide scale, to identify all the mediators conforming to the defined characteristics of the factor that depresses the function of the heart muscle. This led to the finding that interleukin-6 is a major myocardial depressant factor in meningococcal septic shock."

The discovery is the culmination of several decades of research by numerous teams of scientists that have tried to identify the substances that are released into the bloodstream when septic shock develops, damaging the heart muscle's ability to contract. Previous attempts to pin down the molecules responsible had come up with inconclusive data, possibly because there are many different causes of septic shock. The team led by Michael Levin decided to concentrate on a single cause of septic shock, which normally affects healthy people without other medical or surgical conditions.

They focused on meningococcal sepsis, the most frequent infectious cause of death in children in the UK, with death often occurring as a result of myocardial failure. The organs of patients who are severely affected suffer low oxygen levels caused by low blood flow, with subsequent organ failure.

Pathan had shown that if she added plasma taken from children with meningococcal disease to isolated rat myocytes (heart muscle cells), the cells' ability to contract was impaired. She also separated the proteins present in the children's plasma according to size, using chromatography, and worked out the size, molecular weight and charge of the protein present in the fraction that had the observed effect on rat myocytes.

The researchers used high-density gene microarray expression profiling to identify the genes, based on what they knew about the size and chemistry of the protein. The experiments allowed them to identify more than 170 genes that became more active following exposure of the blood cells to meningococci. Of that number, six fit their other criteria. Further experiments helped them to eliminate five, leaving IL-6 as the prime suspect.

They then checked the serum concentration of IL-6 in 140 patients admitted with severe meningococcal disease. Patients with more severe disease, and those with greater myocardial dysfunction, were significantly more likely to have higher serum concentrations of the cytokine.

Paving way for tissue engineering market

Although the European Union estimates world sales for tissue-engineered products at only some EUR 60 million in 2002, European Research Commissioner Philippe Busquin has announced plans to win a major stake for European firms as the market expands to a predicted EUR 4 billion by 2007, and subsequently to EUR 400 billion and beyond. "We may be years away from being able to grow replacement organs, but the progress in research has already resulted in the creation of a new commercial biotechnology sector in Europe," Busquin said, unveiling a new EU study of the sector. The study suggests there are 113 companies active in the field in Europe, with 39 based in Germany, 18 in the UK, and 10 in France and Sweden and six in the Netherlands. Most of them are biotechnology companies, with a quarter from the medical device or pharmaceuticals sectors, and most have fewer than 50 employees.

Looking beyond the current range of tissue-engineered products such as artificial skin, cartilage and bone, the study predicts the emergence of more complex products in cardiovascular and central nervous system indications. It raises the prospect of tissue-engineered heart valves, vessel grafts and heart muscle tissue, or treatments for Alzheimer's disease and Parkinson's disease, and for damaged nerve fibers and spinal cord injury. Further ahead, the report authored by Anne-Katrin Bock, of the EU's Institute for Prospective Technological Studies suggests the construction in vitro of human organs to overcome the scarcity of donor organs and to improve treatment of diseased urinary bladders, kidneys, hearts, livers and pancreases.

Busquin says he is taking action to help tissue-engineering companies overcome the challenges they face because of uncertainties in market development, and non-reimbursement of their products by health insurance systems. He recognizes that the small biotech companies involved do not have the resources for large, long-term clinical trials to provide information on the cost-effectiveness of the treatment compared to conventional alternatives. And, the study said, the lack of cost-effectiveness data is the main reason insurance companies refuse to reimburse treatment with tissue-engineered products.

The key difficulty, in Busquin's view, is the lack of a coherent European regulatory framework, saying divergent European regulations are "an obstacle to the growth of tissue-engineering markets in Europe." His staff is starting to prepare legislation to harmonize authorization procedures for products "and processes based on human tissue engineering." The plan is to provide a set of common rules to clarify the situation for business operators, as well as guaranteeing safety for users and patients. Common rules will allow tissue-engineered products to circulate freely within the EU market.

Consulting firm adds medical device practice

Bionest Partners (Paris), a provider of advisory and management services to life science companies, has formed a medical device practice through which it will offer services in both overall consulting and related advisory services, along with basic corporate finance functions. Heading the new practice is Olivier Pilley, associate member of Bionest. Pilley has 17 years of experience in the medical device industry, holding a variety of corporate positions in cardiology, healthcare e-business and blood treatment. Most recently, he was executive vice president of Fresenius Hemocare, the European leader in plasmapheresis therapies, with management responsibility for the company's International Business Unit. Prior to Fresenius, Pilley led a project of e-procurement for hospitals in France following a 13-year stint at Ela Medical, a European leader in cardiac rhythm management and diagnostic systems, where he was marketing director, Asia-Pacific sales director and director of business development.

Alain Gilbert, managing partner at Bionest, said, "Olivier's experience will be a cornerstone of our new activities as we continue Bionest's rapid expansion by launching [this] new practice." He noted that medical devices have been "a steady growth area while other sectors have been more volatile, and with new technologies entering the field, it is an area that is of increasing interest to our clients, large and small, particularly as U.S.-based companies are entering the European market."

Citing Bionest's "highly successful first year of activity," Gilbert said the creation of the medical device practice "will ensure [that] we continue to grow and bring advisory and management services to the many medical device companies out there in the field." He noted that the new practice can bring "valuable know-how and experience to bear" in areas such as technological assessment, meeting medical and public authorities, and market entry in Europe. "Many new devices come from the ideas of practitioners," Gilbert said, "but these need to be developed into a device that meets the requirements of the whole medical community. [We] can help in gathering valuable opinions and comments from key opinion leaders to validate and improve the future potential of an innovative technology before rushing into production."

Saying that understanding healthcare budget constraints "can often make the difference between success and failure," Gilbert said Bionest "organizes preparatory meetings with authorities in order to fully comprehend their requirements for regulatory and reimbursement processes." This avoids the risk, he said, of producing and filing applications or proposals that may be rejected.

Gilbert said European market structure and EU regulations "have their own specific characteristics," but that the time to market "is significantly shorter than in the U.S. and may allow American companies to generate revenues and to gather clinical data in parallel or in advance of their U.S. operations." He said Bionest helps U.S. firms prepare for entry into Europe "by assessing the best model and implementing the [necessary] pre-launch steps." He said the company "also has the expertise to assist in selecting the optimal EU headquarters location and coach managers in their first steps into European markets."

Bionest now has three practices, with the others being focused on pharmaceutical/specialty pharmaceuticals, and biotechnology and related start-up company activities.

New embolic coil line gets CE mark

Micro Therapeutics (MTI; Irvine, California) has received CE mark approval for its Sapphire NXT line of detachable embolic coils, allowing their sale in Europe. The coils are used in the interventional treatment of brain aneurysms. The NXT line of embolic coils incorporates what MTI refers to as "an innovative surface technology" and will be available, it said, in a broad range of coil configurations similar to that of the original Sapphire embolic coil line.

Tom Wilder, MTI president and chief executive officer, said the Sapphire NXT line "is a result of our ongoing research and development activities to advance embolic coil technology. We have received very positive feedback from physicians who have used NXT in the pre-clinical setting and look forward to introducing this product in Europe through our distributor, ev3 International [Plymouth, Minnesota]."

Micro Therapeutics said the Sapphire NXT product line would replace the original Sapphire line of embolic coils that currently are enjoined from being sold in most European countries due to a patent dispute with the regents of the University of California (Oakland, California) and Boston Scientific (Natick, Massachusetts).

HeartSafe services are launched in UK

Cardiac Science (Irvine, California), a maker of automated external defibrillators (AEDs), has launched its HeartSafe Workplace AED/CPR training and program management services in the United Kingdom. The expansion to the UK follows the company's acquisition last October of Complient (Cleveland, Ohio), a provider of workplace AED/CPR training and program management services, and the successful launch of its direct sales operation there during 2003.

Raymond Cohen, chairman and chief executive officer of Cardiac Science, said the decision to expand its service offering in the UK is a logical step for Cardiac Science following the successful pairing of those services with AED product sales in the U.S. Referring to the United Kingdom as "the largest AED market outside of the U.S.," Cohen said, "we feel strongly that bundling our services, especially in the corporate and government workplace segments, will allow us to increase revenue and gain market share." He said there has been demand for AED/CPR training and program management programs in the UK market since Cardiac Science began direct sales efforts there last year.

CHF therapeutic receives CE mark

Vasogen (Mississauga, Ontario) has been granted CE mark approval for its lead product, Celacade immune modulation therapy, for the treatment of chronic heart failure (CHF). The approval allows the marketing of Celacade in the 15 member countries of the European Union, where the number of persons affected by CHF is estimated at more than 5 million. Vasogen said it plans to launch Celacade in Europe upon the completion of its ongoing pivotal phase III ACCLAIM trial in patients with advanced chronic heart failure.

"Receipt of regulatory approval . . . underscores the excellent safety profile of our product and enables Vasogen to launch Celacade in the second-largest healthcare market in the world, following the successful completion of the company's pivotal Phase III ACCLAIM trial," said David Elsley, president and chief executive officer. He said the approval also strengthens the company's position in ongoing partnering discussions.

The 2,000-patient ACCLAIM trial is designed to support regulatory approvals and the commercial introduction of Celacade in both North America and Europe. Vasogen's previous Phase II trial demonstrated a significant reduction in the risk of death and hospitalization among advanced heart failure patients receiving Celacade.