BB&T European Editor and Staff Reports

Use of implantable cardioverter defibrillator (ICD) gained increasing acceptance in Europe since 2004, jumping 75% from 80 device therapy procedures per one million people to 140 per million in 2008, according to a study published in the European Journal of Heart Failure.

Yet more advanced cardiac resynchronization therapy (CRT) pacemakers, used in combination with an ICD to correct dyssynchrony and prevent sudden cardiac death, recorded a 115% increase from 46 per million in 2004 to 99 per million in 2008.

The combined CRT/ICD therapy is now being used in Europe “on a large scale, increasingly being used as an adjunct to traditional drug treatment,“ according to the report

A study presented at the 2009 European Society of Cardiology Congress in Barcelona found that CRT combined with ICD decreased the risk of heart failure events even in relatively asymptomatic patients with a 34% reduction in the risk of all-cause mortality or heart failure.

The authors of the journal article note reports have described these two devices as a revolution in heart failure with one significant study cited in the most recent guidelines on heart failure suggesting implantation of an ICD was associated with a 23% reduction in all-cause mortality.

Led by Dirk Van Veldhuisen, MD, with the CardioVascular Centre at the University Medical Center Groningen (Groningen, the Netherlands), the investigators for the published article “Implementation Of Device Therapy for Patients with Heart Failure in Europe“ studied ICD/CRT use in 15 European countries.

Any healthcare statistic citing an average for Europe must quickly be qualified as the so-called unified market is an amalgam of countries with independent medical societies issuing guidelines and single-payer systems with markedly different rules for reimbursement.

The study found highest rate of ICD implants was in Germany with 264 per million in 2008, followed by Denmark and the Netherlands. The lowest use of implants was recorded in Spain with 63 per million, Portugal with 68 per million and the UK with 74 per million.

The authors suggest there is an underuse of cardiac therapy devices in many of the countries surveyed citing another study that found “a big gap between the number of patients who fit the criteria for ICD implantation and the number who actually get such a device.“

Based on a calculation of heart failure prevalence between 2% and 3% for the general population, the investigators estimate that around half of these patients potentially could present with an indication for an ICD, an astounding 10,000 per million population.

They note current data suggest that even where ICD/CRT usage is highest at 250 per million population, just 2.5% of those thought eligible are actually receiving an ICD today.

Suggesting that cost and different healthcare systems may explain some of the discrepancies in usage, author van Veldhuisen said, “we still have no clear cost-benefit analysis of more widespread use.“

“Certainly, implantable devices are expensive, and, if we follow the guidelines, the cost implications will be substantial,“ he added.

Heart failure is by far the single biggest reason for acute hospital admission, according to the authors.

Almost 30 million people in Europe experience heart failure and the rate of incidence is still increasing as more cases are being identified, more people are living to an old age, and more are surviving a heart attack but with damage to the heart muscle, they note.

Other countries reporting data for the study that ranked between the highest usage and the lowest included Austria, Belgium, Finland, France, Ireland, Italy, Norway, Sweden, and Switzerland.

BMD wins capital injection, new management

An established in vitro diagnostics (IVD) company that, according to a majority shareholder, “had lost its way in recent years,“ recently reported receiving a e3 million ($4.5 million) injection of capital led by two Paris-based funds specializing in life sciences.

The investment makes Truffle Capital and AGF Private Equity majority shareholders of Biomedical Diagnostics (BMD; Paris).

Philippe Pouletty, MD, the General Partner of Truffle Capital told Biomedical Business & Technology that he has been serving as the acting CEO of BMD since September 2009 and that a new chief executive will be brought on board before the first of the year.

“BMD now has a renewed and driven management and a far more operational board,“ Pouletty said.

BMD was founded in 1986 as a spin-off from Abbott Diagnostic (Rungis, France) and Luminex (Austin, Texas) to develop, produce and market innovative auto-immunity and infectious disease diagnostics.

In 2003 BMD launched the FIDIS system based on the Luminex xMAP technology, and the next year launched the CARIS system, which is considered the standard in immunofluorescence automated testing.

BMD derives 25% of revenues from in-house production while the remaining 75% of sales come from distributing other manufacturer's products.

While BMD has built a sales network in Europe, Australia, and Latin America, France and Belgium remain its strongest markets, and the company leads in autoimmunity disease diagnostics in France with a 40% market share.

The company reported sales of e15.7 million ($20.5 million) in 2006 but has seen a steady decline in revenues, reporting e12.2 million ($17.2 million) at the end of 2008. Dollar values are based on historic exchange rates.

Acknowledging the decline in sales, Pouletty said that since becoming the acting CEO in September, BMD has greatly improved its gross margin, decreased headcount and has streamlined its portfolio to eliminate costly products and refocus on core strengths in auto-immune diagnostics.

Explaining the takeover of a majority position with an investment representing less than one-fourth of sales, Pouletty said, “When a company urgently needs cash, the key is who can make decisions and act quickly?“

“Those who cannot see their shares diluted,“ he said.

Moving forward, Pouletty has renewed the commercial strategy and sharpened the focus for research and development.

On the commercial level, BMD is actively seeking alliances with IVD companies, primarily those based in the U.S., to introduce new products into its European distribution network, and potentially to secure manufacturing rights.

While requiring the company to burn cash, Pouletty said the R&D push comes at a “reasonable cost and in a very interesting area of diagnostics for monoclonal antibodies.“

“The drawback of these therapeutics is that after a few weeks patients develop a resistance to the drug, making them ineffective,“ he explained.

“BMD is currently developing monitoring kits to test patient resistance, and even earlier on, to stratify patients who are likely to develop a resistance,“ he said.

“While it is in the class of companion diagnostics, these kits are independent of any pharmaceutical company,“ he added.

In 2008, the French innovation funding agency OSEO awarded e7.9 million ($12 million) in financial support for the Tracker project to develop diagnostic monitoring kits a rheumatoid arthritis therapy.

BMD shares in this research funding with Neovacs, a start-up transferring a technology platform from the Pierre & Marie Curie University (Paris) for a drug discovery and development program around cytokine targets.

In the Tracker project, BMD is developing a therapy-specific diagnostic as part of an overall patient management strategy, validating its tools for detecting drug-neutralizing antibodies in conjunction with Neovacs' active anti-TNF (tumor necrosis factor) immunization approach to treatment of rheumatoid arthritis patients.

Truffle Capital is an investor in Neovacs and Pouletty is a member of the company's board.

Supersonic inks Japanese accord with Canon

SuperSonic Imagine (Aix-En-Provence, France) said it has signed an exclusive distribution agreement with Canon Marketing Japan (Canon MJ; Tokyo) to develop the Japanese market.

After receiving CE approval and FDA 510(k) clearance for its Aixplorer MultiWave Ultrasound System, SuperSonic has developed commercial networks on four continents and in more than 30 countries.

“The agreement with Canon MJ is quite important to us as it opens the door to one of the largest ultrasound markets in the world. In order to assess our product in this very competitive market, having Canon MJ as a partner is essential. I see our relationship with Canon MJ as a long-term collaboration extending potentially to other domains in the future. Aixplorer, with its unique disruptive technology, is well suited for markets looking for new innovative approaches,“ said Jacques Souquet, CEO of SuperSonic.

The Aixplorer is the only commercially available system of its kind with MultiWave Technology, which is based upon the interaction between conventional longitudinal waves and shear waves in tissue. The system consists of an all software-based architecture which provides both B-mode images and, for the first time, uses shear waves (ShearWave Elastography) to quantify true tissue stiffness or elasticity information in kilopascals. With MultiWave Technology, the Aixplorer brings clinicians significantly enhanced real-time diagnostic information that the company said is quantitative and reproducible.

NIMS gets Canadian patent for Exer-Rest

Non-Invasive Monitoring Systems (NIMS; Miami) reported that the Canadian Patent Office issued Patent number 2,534,302 to NIMS on Oct. 20. The patent, titled “Reciprocating Movement Platform for the External Addition of Pulses to the Fluid Channels of a Subject,“ relates to the comprehensively researched technology underlying NIMS' Exer-Rest acceleration therapeutic platform. The Canadian patent that expires Aug. 4, 2024 incorporates 55 claims dealing with treatment of acute and chronic inflammatory diseases and is the Canadian counterpart to U.S. Patent No. 7,404,221, the fifth patent issued for this technology.

NIMS is authorized to sell the Exer-Rest in Canada as a class II medical device with CE certification. The Exer-Rest is intended as an aid to improve circulation, increase joint mobility, and to provide temporary relief of minor aches and pains.

The Exer-Rest is currently sold in the U.S., Canada and other major international markets. It is FDA cleared as an aid to temporarily increase local circulation, to provide temporary relief of minor aches and pains, to reduce morning stiffness and to provide local muscle relaxation. The Exer-Rest is also approved for sale in Europe as an aid to increase mobility.

Pall opens European HQ in Switzerland

Pall (Port Washington, New York), a developer of filtration, separation and purification technology, reported the opening of its European headquarters in Fribourg, Switzerland. The office will initially house Pall's Life Sciences business in Europe, with plans to integrate the company's European Industrial business in 2011. The initiative was undertaken with the Fribourg Development Agency.

“Europe represents approximately 40% of Pall's $2.3 billion revenues worldwide. The Fribourg office will manage the company's continuing growth in the European markets and bring important efficiencies to customers and the business,“ said Eric Krasnoff, Pall chairman/CEO.

Agilent names 1st SureSelect Euro CSP

Agilent Technologies (Santa Clara, California) reported that Fasteris (Geneva) has been named the first European Certified-Service Provider (CSP) for Agilent's SureSelect Target Enrichment System for next-generation sequencing.

SureSelect, introduced last February, has been shown to greatly increase the speed and cost-efficiency of next-generation sequencing workflows used in life science research by enabling experiments to focus on genomic regions of interest rather than sequencing the entire genome.

Fasteris achieved CSP status for the SureSelect system after demonstrating a high level of proficiency using the SureSelect system with the Illumina (San Diego) Genome Analyzer.

The SureSelect system is based on an in-solution design, making it automation-friendly and easily scalable from ten reactions through thousands.

Users can design their own custom SureSelect kits using Agilent's eArray online design tool, which contains many key genomes and also lets users upload their own sequences. Because sample requirement is 3 micrograms or less of gDNA, researchers can perform highly targeted next-generation sequencing on very precious samples.

Agilent and Illumina have a non-exclusive co-marketing agreement to support the SureSelect Target Enrichment System optimized for the Illumina Genome Analyzer.

Sorin reports 1st patient in Clepsydra trial

Sorin Group (Paris) reported the first inclusion of a patient in the Clepsydra clinical trial. The study will investigate the sensitivity to changes in heart failure status of PhD, a unique diagnostic feature using the dual sensor technology of minute ventilation and accelerometer to monitor patient's breathing and activity levels every day.

The algorithm aims to provide physicians with both trends and indicators in order to highlight sustained changes in overall health status that could relate to heart failure (HF) evolution.

PhD is available in the Paradym family of ICDs in Europe and under clinical evaluation in Implantable Cardiac Resynchronization Therapy Defibrillators in Europe and U.S.

As the severity of HF can fluctuate and drug therapies adjusted to improve the patient's condition, it is important to monitor recognized indicators of disease progression to prevent the patient being hospitalized. PhD measures activity workload and ventilation at rest and exercise, which are two key measurements to indicate that a patient's heart failure condition is progressing. The Clepsydra study will test the PhD algorithm that is designed to give advance notice of sustained deterioration. Advanced warning at follow-up could give physicians time to intervene in the patient's treatment to avoid the costs and patient burden associated with hospitalization.

The Clepsydra study, will evaluate PhD in 550 patients to be enrolled in the U.S. and Europe. Patients will be closely monitored over a minimum of 13 months by hospital visits and by telephone checks.

Andrew Kaplan, MD, cardiac electrophysiologist with CVAM, CardioVascular Associates of Mesa, at Mountain Vista Medical Center (Mesa, Arizona), performed the first implant.

MagForce submits product file for CE mark

MagForce Nanotechnologies (Berlin) has submitted the product file for NanoTherm to Medcert GmbH, the medical certification and testing company that serves as notified body for the certification of medical products.

With this step, MagForce said it has now commenced the conformity assessment procedure for its Nano-Cancer therapy. Following successful completion of this conformity assessment procedure and EC type testing of the magnetic field applicator, MagForce will be able to apply the CE European conformity marking and to market its Nano-Cancer therapy throughout the European Union.

In early November, the results of a pivotal clinical trial were published demonstrating the efficacy of the new therapy in patients with recurrent glioblastoma, and it is upon these results that the application for European regulatory approval is based. The primary study objective, which was to extend the median survival time following tumor recurrence by three months compared to a historical control group, was significantly exceeded in the actual results. Following treatment with Nano-Cancer and accompanying radiotherapy, the median survival time following diagnosis of the first tumor recurrence was 13.4 months. Compared to the 6.2-month median survival time following recurrence observed in a recently published EORTC study, the patient survival time was shown to be statistically highly significant longer.

MagForce says its Nano-Cancer therapy allows the targeted destruction of tumors using superparamagnetic nanoparticles to generate heat.

Absorber gets patent protection for XM-One

AbSorber (Stockholm, Sweden) has received patent protection for its transplantation cross match-test XM-ONE in the European countries. The patent was recently approved in New Zealand, which was the first country to approve a patent for AbSorbers product. The European countries are highly prioritized markets for AbSorber and the patent approval is an important milestone in Absorbers intellectual property strategy.

AbSorber said it also has patent applications pending for XM-ONE in the U.S., Japan and other key transplantation markets. The company expects more countries to follow the European approval of the XM-ONE patent.

XM-ONE is the first standardized test designed to detect antibodies against the cells that line the inside of blood vessels. These endothelial cells are the first point of contact between the transplanted organ and the recipient's immune system. Anti-endothelial cell antibodies have been shown to play a key role in causing post-transplantation rejections.