Type II Diabetics Treated with Bydureon Experience Reduced Cardiovascular Risk Factors

The Medical Technology Blog

Drug Delivery Insight – Research & Development

Amylin Pharmaceuticals, Eli Lilly and Alkermes have revealed new analyses from the DURATION-3 and -4 trials showing patients treated with the investigational medication Bydureon (exenatide extended-release for injectable suspension) experienced significant improvements in select cardiovascular (CV) risk factors, in comparison with patients who received commonly prescribed diabetes treatments. The analyses showed that patients receiving Bydureon for the treatment of Type II diabetes experienced improvements in composite endpoints related to body weight, abnormal blood pressure and abnormal lipid levels.

The initial DURATION-3 trial was an open-label study of 467 patients not achieving adequate glucose control using metformin therapy alone or in combination with a sulphonylurea. Subjects were randomised to receive treatment with Bydureon or titrated doses of Lantus (insulin glargine, Sanofi). The primary endpoint was reduction in A1C; secondary endpoints included change in body weight along with other parameters of glucose control, safety endpoints including hypoglycaemia, CV risk biomarkers and patient-reported outcomes.

Interim results from DURATION-3′s ongoing extension found that patients receiving Bydureon and completing 84 weeks of therapy showed statistically significant reduction in body weight (vs Lantus; treatment difference: 9.8 lbs). There was also, statistically significantly more patients in the Bydureon treatment arm met a composite endpoint of A1C <7 per cent plus target systolic blood pressure (<130 mmHg) and LDL cholesterol (<100 mg/dL) (15.7 per cent vs 7.9 per cent with Lantus); and met a composite endpoint of A1C<=6.5 per cent plus target systolic blood pressure (<130 mmHg) and LDL cholesterol (<100 mg/dL) (11.2 per cent vs 5.1 per cent with Lantus).

The 26-week, double-blind, randomised, four-arm parallel DURATION-4 study enrolled 820 drug-naive patients with Type II diabetes and compared Bydureon with metformin, Januvia (sitagliptin, Merck & Co) and Actos (pioglitazone HCI, Takeda) monotherapies. The primary endpoint was reduction in A1C levels, while secondary endpoints included change in body weight along with other parameters of glucose control, CV health and patient-reported outcomes. The post hoc analyses showed patients treated with Bydureon or metformin were more likely to achieve clinically relevant composite goals than patients treated with Actos or Januvia. Researchers evaluated how many patients in each treatment group achieved a composite endpoint of A1C<7 per cent, no weight gain and no minor or major hypoglycaemia (48 per cent for Bydureon vs 22 per cent for Actos, 35 per cent for Januvia and 46 per cent for metformin); and reached a composite endpoint of A1C<7 per cent plus target systolic blood pressure (<130 mmHg) and target LDL cholesterol (<100 mg/dL) (16 per cent for Bydureon vs 10 per cent for Actos, 7 per cent for Januvia and 13 per cent for metformin).

In the DURATION-3 study, gastro-intestinal adverse events were among those most commonly reported; however, the number of new cases of all adverse events declined during the extension phase of the trial. In the DURATION-4 study, the most frequently reported adverse events among Bydureon users were nausea and diarrhoea. These data are consistent with the previously reported profiles of Bydureon and Byetta (exenatide) injection.

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Researchers create human heart cells that can be paced with light

The Medical Technology Blog

This weeks artice on the Medical Technology Blog is taken fromEspicom’s business publication, Cardiovascular Device Business, please read on…

In a paper published in the September issue of the Biophysical Journal, lead author Dr Oscar Abilez, a postdoctoral scholar and PhD candidate in bioengineering, and a multidisciplinary team from Stanford University, describe how they have, for the first time, engineered human heart cells that can be paced with light using a technology called optogenetics. In the near term, the researchers say the advance will provide new insight into heart function. In the long term, however, the development could lead to an era of light-based pacemakers and genetically matched tissue patches that replace muscle damaged by a heart attack.

To create the light-responsive heart cells, the researchers first inserted DNA encoding a light-sensitive protein called channelrhodopsin-2 (ChR2), into human embryonic stem cells. ChR2 controls the flow of electrically charged ions into the cell. For heart cells, the primary ion is sodium, which initiates an electrochemical cascade that causes the cell to contract. They then transformed the optogenetically engineered stem cells into cardiomyocytes those that respond to light.

The key protein for the experiment is ChR2, which is sensitive to a very specific wavelength of blue light and regulates tiny channels in the cell surface. When ChR2 is illuminated by the right wavelength of blue light, the channels open to allow an influx of electrically-charged sodium into the cell, producing a contraction. After creating the cells in a laboratory dish, the researchers tested their new cells in a computer simulation of the human heart, injecting the light-sensitive cells in various locations in the heart and shining a virtual blue light on them to observe how the injections affected contraction as it moved across the heart.

In a real heart, the pacemaking cells are on the top of the heart and the contraction radiates down and around the heart. With these models, the researchers say they can demonstrate not only that pacing cells with light will work, but also where to best inject cells to produce the optimal contraction pattern.

The long-term goal is the development of a new class of pacemakers. At present, surgically-implanted electrical pacemakers and defibrillators are commonplace, regulating the pulses of millions of faulty hearts around the world. However, Abilez adds that neither is without problems – pacemakers fail mechanically and the electrodes can cause tissue damage. Defibrillators, on the other hand, can produce tissue damage due to the large electrical impulses that are sometimes needed to restore the heart’s normal rhythm. In the future, the researchers envision that bioengineers will use induced pluripotent stem cells fashioned from the recipient’s own body, or similar cell types that can give rise to genetically matched replacement heart cells paced with light, circumventing the drawbacks of electrical pacemakers.

Co-author, Dr Christopher Zarins, professor emeritus of surgery and director of the lab, speculates the the work could result in a pacemaker that is not in physical contact with the heart. Instead of surgically implanting a device that has electrodes poking into the heart, engineered light-sensitive cells would be injected into the faulty heart and used to pace the heart remotely with light, possibly even from outside of the heart. The leads for such a light-based pacemaker might be placed outside the heart, but inside the pericardium, the protective sack surrounding the heart. Another concept to be explored is a pacemaker placed inside the heart chambers, as with traditional pacemakers, whose light can travel through the intervening blood to pace light-sensitive heart cells implanted inside. Since the new heart cells are created from the host’s own stem cells, they would be a perfect genetic match.

The authors conclude that optogenetics could also lead to advances beyond the heart. It might lead to new insights for various neuronal, musculoskeletal, pancreatic and cardiac disorders, including depression, schizophrenia, cerebral palsy, paralysis, diabetes, pain syndromes and cardiac arrhythmias.

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The Medical Technology Blog

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In the Medical Technology Blog today’s post is and article taken from Espicom’s business publication Drug Delivery Insight, provided by DDI’s editor, Sophie Bracken, please read on…

A new international pharma company has been launched, the result of a three-year Anglo/Russian project by London, UK’s Celtic Pharma. The company, Pro Bono Bio, has big growth targets that, if attained, could to allow it to combine global pharma expertise from within the UK together with international capital and funding from the Russian Corporation of Nanotechnologies (RUSNANO).

Pro Bono Bio has decided on a clear humanitarian approach to its business, namely that its products will be priced in different geographic areas based on the region’s ability to pay. Backed by company’s shareholders, the business model includes the provision of free drug donations to Africa, based product sales at normal prices in the Western European pharma market.

The UK’s Prime Minister, David Cameron believes that the Pro Bono project is “a great example of UK/Russia collaboration at the cutting edge of R&D, demonstrating how British business can work together with their Russian counterparts to expand into new areas, creating jobs and prosperity in the UK”.

As well as keeping busy with its humanitarian focus, Pro Bono has released its first prescription medicine in the UK known as Flexiseq. The latter is a nanotechnology-based osteoarthritis treatment, and the first in a pipeline of products under development. The company has plans to roll out a further two more products in the UK – Exoseq and Possoseq – over the coming months. The products are designed for the treatment of inflammatory skin disorders, including psoriasis and eczema. Like Flexiseq, they are based on Pro Bono’s Sequessome technology, which physically absorbs and removes chemicals that are a key component in the pain and inflammation cascade. Sequessomes were invented and developed by Pro Bono with the help of external partners, and the technology is protected by a number of worldwide patents.

Other products that Pro Bono has in the pipeline include blood factors for the treatment of haemophilia, and novel antibiotics for the treatment of serious infections like C. difficile, MRSA and tuberculosis. Pro Bono has big plans to develop and market these products by exploiting its management team’s so-called “Big Pharma” experience – expertise from the likes of the company’s CEO, John Mayo.

First off, Pro Bono will focus on marketing Flexiseq and other Sequessome Technology-based products in Western, Central and Eastern Europe as well as the CIS. The company’s commercial and manufacturing model is based on collaborations with specialist service partners. The outsourced sales model will eventually be bolstered by selective full ownership of the salesforce in certain territories. Also, products will initially be sourced from European and Russian manufacturers’ approved facilities.

In the mid-term, Pro Bono will support the plans by building  – with RUSNANO’s support – a state-of-the-art pharma plant close to Moscow, with a further plant in the UK, in order to comply with EU regulations.

To purchase the latest drug delivery report from Espicom Business Intelligence, detailing an examination of the trends and advances in the three major drug delivery sectors, Lipid-based, Polymer-based, and Biovectors, please click on the link below:

Emerging Drug Delivery Technologies & Strategies – Players, Pipelines & Partnerships


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US joint replacement registry gets fully under way

The Medical Technology Blog

Hi and welcome back to the Medical Technology Blog, and today’s post come from Espicom’s excellent news publication, Orthopaedic Business News, please read on…

Like the National Joint Registry of England & Wales before it, the American Academy of Orthopaedic Surgeons (AAOS) has been busy with the task of establishing the American Joint Replacement Registry (AJRR) – a project designed to collect data on all primary and revision total joint replacement procedures in the US. The registry’s mission is to improve patient safety and quality of care, as well as reducing the associated cost. With that mission in mind, the AJRR has recently completed its pilot programme of data collection.

Dr John Callahan, Vice President of AAOS and team leader of the AJRR project, said that past medical registries have been shown to help reduce the cost of medicine and, in particular, the burden of joint replacement. Callahan believes that decreasing revision surgeries by half would save millions anually for healthcare payers as well as for the US government. “Because of this, US Congress is interested in including registries in healthcare reform. The AJRR will be able to provide information in a timely manner, where it can be analysed by orthopaedic surgeons”, he said.

Short-term, the registry aims to establish an infrastructure and a uniform system for the collection of information and monitoring outcomes of total joint replacement in the US, as well as identify patients who may need follow-up evaluation, thereby increasing patient safety. Long-term, the registry’s goals are to create a real-time feedback mechanism in order to detect “sub-optimal” performance, and establish a uniform system that can be used to expand understanding of total joint replacement for research to improve patient care.

AAOS statistics show that in 2006 alone, more than one million hip and knee replacement took place in the US. Of these, around 7.5 per cent were revision surgeries, resulting in 77,000 procedures, at a cost of over US$3.2 billion. The AAOS has projected that the AJRR will reduce healthcare costs by around US$1.3 billion over the next 20 years. The AAOS believes that even a 2 per cent decrease in revision rates could potentially save US$65.2 million a year. Similar registries in Sweden, England & Wales, Canada and Australia have seen up to a 10 per cent reduction in revision rates as a direct result of their own registries.

However, the registry is not all about saving cash. Explaining the registries main aims and focus points, Dr David Lewallen, Chair of the AJRR Board of Directors, said there is a national interest in registries, particularly how patients will benefit. In the past, national data collection of hip and knee implants has helped to improve care by allowing surgeons, device manufacturers and hospitals to better understand what aspects of joint replacement is successful, and what needs to be improved. Lewallen said that the AJRR will enable surgeons, hospitals and device manufacturers to review their own data and compare their performance with similar institutions, in order to understand where opportunities for improvement may exist. The registry will also be a resource for patients, who will be able to contact the registry to find out what methods and devices were used at the time of their surgery.

The AJRR aims to gather data on all replacement and revision surgeries, including younger patients who are not recipients of Medicare – with the ultimate goal of achieving 90 per cent participation. The AJRR was set up in June 2009, and enrolment began in 2010. Participating hospitals have been submitting data for only a few months, but already information on over 3,600 primary and revision replacements has been assembled from eight different reporting sites, marking the culmination of the pilot stage.

Following an updated report on the pilot project, covering lessons learned and data analysis, the AJRR Board of Directors have begun formulating strategies for outreach recruitment, expanding resources and efficient data collection methods as the registry moves to full production. The AJRR’s timeline for 90 per cent participation in the registry is for October 2013.

At the moment, the AJRR is focused on collecting so-called “level-one” data, which includes a number of core data elements, such as patient, surgeon, procedure and hospital data. Each patient, surgeon and hospital has a unique identifier, which enables index procedures to be linked to subsequent events, permits patients to access their own information, allows data to be linked to other databases and helps maintain confidentiality.

Level-two data include variables that could enhance the value of the data analysis and allow risk adjustment, such as the patient’s body mass index and any comorbidities, as well as process of care data such as antibiotic prophylaxis. Level-three data will focus on outcomes and patient satisfaction, while level-four data (such as radiographs) provide more in-depth analysis of why and how implants or procedures fail.

Lweallen said the next step of the AJRR is to recruit a Medical Director to supervise operations. The registry is also moving toward implementing systems that will enable a wide range of hospitals and systems to submit data.

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NICE delivers its verdict on next-generation cardiac CT scanners

The Medical Technology Blog

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Medical Industry Week News

It’s good news this week for some of the biggest medical imaging companies

GE Healthcare, Siemens Healthcare, Philips Healthcare and Toshiba Medical Systems – with all four receiving tentative backing for their respective next-generation cardiac CT scanners in draft guidance drawn up by the National Institute for Health and Clinical Excellence (NICE) in its latest draft guidance on the subject.

Now available for a period of public consultation, the draft guidance specifically applies to the use of the Somatom Definition Flash CT scanner (Siemens), Aquilion One (Toshiba), Brilliance iCT (Philips) and Discovery CT750 (GE) in the NHS in England for people with suspected or known coronary artery disease (CAD) in whom imaging is difficult with earlier generation CT scanners. A review team looked at 24 studies, with the vast majority (20) using Siemens’ Somatom Definition Flash (1) or an earlier model, Somatom Definition (19). Interestingly, despite its glowing endorsement only two of the studies referenced actually used the cutting edge CT scanner technology. In 2007, CAD was estimated to have claimed 91,000 deaths in the UK.

CT scans are performed to evaluate the arteries of the heart, and can also be used to assess the function of the heart, the anatomy of the heart, and the degree of coronary calcification in the heart. The technology survived a review of five recognised models for assessing the cost effectiveness of next-generation cardiac CT scanners, including the Europa model, for the prognosis of people with CAD, and the York Radiation Model, which estimates the impact of imaging in terms of radiation dose on cancer mobidity and mortality.

The recent NICE clinical guideline on chest pain recommends CT coronary angiography and invasive coronary angiography to assess the state of arteries and identify significant narrowing in people with an estimated probability of coronary artery disease of 10 to 29 per cent and a calcium score of <400 or less. People with a calcium score >400 are considered difficult to image using earlier generation CT technologies. Other reasons that make CT imaging difficult are obesity, arrhythmias (irregular heart beat), high heart rates (above 70 beats per minute) or previous coronary stents or bypass grafts.

The latest generation cardiac CT scanners have technical features that aim to overcome these difficulties, including the ability to acquire images much faster than earlier generation CT scanners, better image quality and reduced radiation doses. The NICE guidance recommends the use of these scanners for first line imaging of the coronary arteries in people with suspected stable coronary artery disease who are difficult to image with earlier generation CT scanners and whose estimated probability of having CAD is 10 to 29 per cent. In addition, the draft guidance recommends their use in people with known CAD for first line evaluation of disease progression to establish the need for revascularisation where imaging with earlier generation CT scanners is difficult.

Imaging companies will not quite be celebrating at the moment as final guidance on this topic is not expected until the new year, but they will be quietly confident that there is now a recognised need for the technology within the National Health Service in the UK.

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Cardiovascular Device Business News

The Medical Technology Blog

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Last post of the week in The Medical Technology Blog comes from the Cardiovascular Device Business, Espicom’s business publication. Please read on…

Swedish researchers compare risk of stent thrombosis and restenosis in new vs old DESs

Findings from the complete Swedish Coronary Angiography and Angioplasty Registry (SCAAR) have demonstrated that percutaneous coronary intervention (PCI) with ‘new generation’ drug-eluting stents (DESs) was associated with a 38 per cent lower risk of clinically meaningful restenosis and a 50 per cent lower risk of stent thrombosis compared with ‘old generation’ DESs.

Although many trials and studies support the overall early- and mid-term safety and efficacy of first-generation DESs, there has been concern regarding their long-term safety, especially regarding the potential risk of late stent thrombosis as well as late restenosis. New drug-eluting stents (n-DESs) have been developed with the purpose of overcoming the current limitations of the older generation drug-eluting stents (o-DESs).

The purpose of this study was to evaluate the long-term outcome in all patients who underwent stent implantation with bare-metal stents (BMS), o-DESs and n-DESs in Sweden, using SCAAR, a national registry with complete consecutive enrolment. The latter holds data on consecutive patients from 29 centres that perform coronary angiography and PCI in Sweden. The registry is sponsored by the Swedish Health Authorities and is independent of commercial funding. The technology is developed and administered by the Uppsala University Clinical Research Center. All consecutive patients undergoing coronary angiography or PCI are included. Information with respect to restenosis and stent thrombosis has been registered for patients undergoing any subsequent coronary angiography for a clinical reason since the beginning of 2004.

The current study included 94,384 stent implantations in Sweden (BMS, n=64631; o-DES, n=19202; n-DES, n=10551), from November 2006 to October 2010. Follow-up was performed up to two years post-intervention. The performance up to two years of different types n-DES was evaluated in an unselected, large, real-world population – including patients with myocardial infarction, three-vessel and/or left main disease, bifurcation lesions, graft disease, restenotic lesions and chronic total occlusions. The main findings from this study are that PCI with n-DESs was associated with a 38 per cent lower risk of clinically meaningful restenosis and a 50 per cent lower risk of stent thrombosis compared with o-DESs. These findings can be useful for the management of patients with a high-risk profile that could benefit more from these new devices.

Further studies are said to be needed in order to attempt to discriminate whether one of the three components of the n-DES – the polymer, the stent alloy, the eluting-drug – is mainly involved in decreasing the incidence of stent thrombosis and restenosis. Improved stent designs with thinner struts and more biocompatible polymers may have an important impact on drug elution profiles, endothelial coverage and functional recovery.

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Non-Surgical Treatment for Varicose Veins

The Medical Technology Blog

As the NHS cuts start to bite, could a treatment for varicose veins provide one of the answers?

Maybe not! But Medical Industry Week this week highlighted the rather grand suggestion that a non-surgical treatment for varicose veins could save the UK’s National Health Service over £17 million annually in healthcare costs, and help 7,000 patients avoid further treatment due to unsuccessful alternative treatments. It’s not going to solve all our problems, but if it’s true then it’s a good start!

All medical device companies like to big up their respective device and technologies from time to time, particularly when one considers that regulatory authorities from across the country are tightening the budgets.  So it remains to be seen whether VNUS’ claims are just marketing puff, but it’s interesting to see how companies are increasingly using costing as a sale push, in addition to all the stated benefits of improving healthcare.

Developed by US-based VNUS Medical Technologies, the VNUS Closure Procedure involves a hospital stay of a couple of hours, treatment under local, rather than general anaesthetic, and claims a much faster recovery time with most patients able to walk out of the treatment room unaided. The procedure is also much less resource-intensive than surgery to the NHS, particularly compared to conventional varicose vein stripping, which takes up a great deal of operating theatre time.

For the same costs, the company said this week that a further 25,000 patients could be treated earlier and avoid pain, or discomfort. Further savings are on offer as the procedure can be carried-out in a treatment room so it has the potential to free-up theatre-time, enabling the NHS to treat other serious conditions more quickly and to reduce those all-important waiting-times.

On its own, the VNUS procedure may not represent a significant dent in the £20 billion of spending cuts that the NHS is faced with securing over the next four years, but getting on top of some of these, arguably less glamorous treatments could collectively make a positive impact on meeting this ambitious target. Medical Industry Week argues that it is time to take a closer look at these sort of treatments in a bid to meet a target that even the NHS Confederation says is unlikely to be achieved with the timescale.

This article was provided by Lawrence Miller, editor of Medical Industry Week, and the medical newsletters teamleader.

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Zimmer’s cash-saving scheme begins with Statesville site closure

The Medical Technology Blog

 Orthopaedics Business News

Zimmer has put the wheels in motion regarding its plan to close its operations in Statesville, NC as part of a restructuring of its manufacturing facilities.

Warsaw, IN-based Zimmer has filed a notice with the North Carolina Department of Commerce of its impending plans, with the first redundancies widely expected to take place in October. The phase-out of the Statesville plant will be completed in March 2012. It is not clear how many Zimmer employees at the plant will lose their jobs, but the site currently employs around 125 people.

The Statesville facility was opened in 1980 and makes tourniquet cuffs, traction devices, slings and braces. The closure is part of Zimmer’s “global restructuring and transformation initiatives” that were unveiled in January this year. The Statesville site closure is part of this strategy that aims to save over US$100 million for the company, which looks set to lose its title of world’s largest orthopaedic company to DePuy by the end of the year. The company has also said it will be “reducing management layers and consolidating global sourcing to drive vendor cost reduction”. This could well mean that in the near future, Zimmer could be axing non-essential executive positions from its Warsaw headquarters, and perhaps even terminating deals it has with component suppliers and distributors, as it strives to save that US$100 million.

thank you to Sophie Bracken, editor of Orthopaedics Business News for providing this article.

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Introducing Espicom Business Intelligence

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Our first video on Youtube;

Please check it out and leave a comment or if you’re in a good mood, give us a thumbs up!

Thanks, Paul.

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Will Axis-Shield give into rising pressure of takeover offer from Alere?

The Medical Technology Blog

Alere, a key player in the rapid point-of-care and laboratory diagnostics market with products that focus on infectious disease, cardiology, oncology, drug abuse and women’s health, has brushed aside negative feedback from Axis-Shield and pushed ahead with a cash offer for the UK-based company.

As part of the offer, Axis-Shield’s shareholders will be offered £4.60 (or approximately US$7.51) for each Axis-Shield share held by them, valuing the transaction at approximately £230 million (or approximately US$375 million). The offer will be conditional upon Alere receiving valid acceptances in respect of not less than 90 per cent of Axis-Shield shares to which the offer relates and not less than 90 per cent of the voting rights carried by those shares.

In June, Alere had made an indicative non-binding proposal to acquire Axis-Shield, however, the latter rejected the proposal and also turned down an offer to conduct further discussions with Alere. At the time, Alere revealed that it was keen to work towards a recommended takeover offer for Axis-Shield and that it would welcome the opportunity to discuss a possible transaction in a constructive manner. The company said its proposal was “a means to facilitate discussions” with Axis-Shield and its shareholders. Now, in a move that adds further pressure on its target, Alere has made an additional open market purchase of approximately 6.4 per cent of Axis-Shield’s share capital.

Axis-Shield is an international in vitro diagnostics company, headquartered in Dundee, UK, with R&D and manufacturing bases in Dundee and Oslo. The group specialises in the supply of instruments and tests for the rapidly growing physician’s office testing market and the development, manufacture and marketing of diagnostic kits in areas of clinical need, including cardiovascular and neurological diseases, rheumatoid arthritis, and diabetes. During 2010, the company made significant advances with the continued growth of its international in vitro diagnostics business and revenues exceeded £100 million for the first time.

Alere believes it’s all cash offer is highly attractive for Axis-Shield shareholders, representing a ‘compelling value proposition’ with a high degree of certainty at a substantial premium to the undisturbed share price. In addition, the company expects Axis-Shield will be complementary to its existing businesses and that it can help develop and grow the Axis-Shield product portfolio to be a clear leader worldwide in its core markets.

Over the forthcoming weeks, the question remains as to whether Axis-Shield will succumb to the pressure to reach an agreement Alere, and whether the latter, with revenues of over US$2.1 billion behind it for 2010, has done enough to win over the UK-based company.

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