The Medical Research Council (MRC) has committed £7m funding to support 15 academic drug research projects using compounds from AstraZeneca.

The collaborations are expected to improve our knowledge of ways to treat major diseases such as dementia and cancer, as well as rare diseases such as motor neurone disease.

AstraZeneca made 22 pharmaceutical compounds, which it had validated as suitable for further research, available to medical researchers in December 2011.

Eight of the research projects will involve clinical trials of new drug candidates, while the other seven will involve laboratory and animal models.

“This landmark collaboration will see our leading scientists working with industry to find new insights into disease,” added David Willetts, Minister for Universities and Science. “It will speed up the search for innovative treatments and keep the UK at the forefront of biomedical research, which will in turn drive growth and deliver benefits for patients.”

The MRC received 23 full funding proposals, which it assessed independently of AstraZeneca. The recipients include research teams at universities in Manchester, Leeds, Sheffield, London, Glasgow, Birmingham, Edinburgh and Bristol.

The announcement was welcomed by the BioIndustry Association (BIA), whose Chief Executive Steve Bates said: “Today’s funding announcement signals the beginning of an exciting coming together of academia, industry and government to create new pathways to develop novel therapies for a range of serious conditions.

“The prospect of de-risking private investment in this way and supporting the development of these products for patients through innovative ways of working shows how the biopharmaceutical sector is responding creatively to the challenge of getting more treatments to market.”

The NHS is placing too much emphasis on ‘breakthrough drugs’ rather than on diverse and incremental innovation, according to the ABPI.

An updated report on pharmaceutical innovation commissioned by the UK trade association warns that by focusing on unique medical solutions, the NHS risks narrowing the scope of medicines.

ABPI Chief Executive Stephen Whitehead (pictured), launching the report, commented: “I fear for the future of UK medical research.”

The Many Faces of Innovation was commissioned by the ABPI from the Office of Healthcare Economics, updating a 2005 report commissioned by EFPIA.

As well as providing new case studies, the updated report places pharmaceutical innovation in the context of the UK health economy of 2012.

The report attacks the dichotomy between ‘breakthrough’ and ‘me-too’ products, arguing that innovation can be incremental – especially where ‘stratified’ medicine is concerned.

In addition, innovation has several dimensions: it could bring “advances in health gains”, “cost savings in health services” or “advances in patients’ and/or carers’ convenience”.

Finally, medical research benefits from multiple companies tackling the same problem – so it’s not helpful for there to be only one ‘winner’.

The report implicitly criticises NICE for assuming that each medical problem has one ‘best’ solution and that ‘value’ has a single metric.

The forthcoming medicine pricing negotiations will mark a watershed for the industry, Whitehead said: “If we minimise the reward for innovation in the UK, then our manufacturers will go abroad. Our industry, our economy, and our healthcare system will suffer – UK patients will suffer.”

UK pharmaceutical companies conducting early stage clinical trials will be able to collaborate more extensively with leading medical academics following the government’s launch of two pioneering partnership programmes designed to accelerate the development of innovative treatments from lab to patient.

The first two National Institute for Health Research (NIHR) translational partnerships – in respiratory and joint-related inflammatory diseases – will give life science companies access to a ‘unique network of top clinical scientists’ in government-funded research facilities, leading universities and the NHS.

The government says the partnerships will also provide unparalleled access to ‘cohorts of well-characterised patients’ – cutting through red tape to speed up the recruitment and testing of NHS patients, and ensuring quicker access to life-changing new therapies.

Access to the Partnerships will be via the NIHR Office for Clinical Research Infrastructure (NOCRI), meaning that when a company wants to collaborate, only one legal agreement is required rather than having to negotiate with each NHS Trust and University.

The new initiative represents an attempt to address a sharp decline in the UK’s reputation as a world-class location for medical research, and also reflect a growing appetite across the pharmaceutical industry to find efficiencies in its R&D model through greater collaboration with external specialists.

David Willetts, Minister for Universities and Science, said the research partnerships would provide a unique model for collaboration between the life sciences industry, the NHS and universities. “They will be a key driver of growth and innovation, reducing the time it takes to translate research into benefits for patients and the economy,” he said.

The ABPI has welcomed the initiative, citing collaborative working with clinical academic investigators as pivotal to the changing model of drug development for the pharmaceutical industry. “Translational Research Partnerships offer an efficient and effective way for companies to work with some of the UK’s leading translational research experts through NOCRI,” said Dr Allison Jeynes-Ellis, Medical and Innovation Director, ABPI. “Companies will see great advantages to working with the partnerships and consequently they will attract ground-breaking research into the UK.”

The government will provide £1.3 million to help set up the first two partnerships; inflammatory respiratory disease and joint and related inflammatory diseases. The NIHR partnership for translational research on respiratory diseases – such as asthma, COPD, allergies, cystic fibrosis and acute lung injury – includes hospitals and universities in Northern Ireland, Oxford, Manchester, Southampton and London. The partnership in joint and related inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, and synovitis, includes Barts and the London NHS Trust, the University of Birmingham, UCLH and Cambridge University.

Terms of the partnership are likely to include identifying more efficient ways of tapping into suitable patient groups for clinical trials, and unlocking funding beyond life science investment in exchange for shared intellectual property rights for any breakthrough discoveries.

Orexo has appointed Peter Edman as its new Chief Scientific Officer, responsible for the company’s research and development division.

Peter currently works as CSO and Head of Research and Development at Sobi (Swedish Orphan Biovitrum).

Anders Lundström, President and CEO of Orexo, said: “Peter Edman has extensive experience in the areas of research and development and leadership. Both his skills in early drug discovery and drug development in late stages will be of great value to Orexo.”

Peter has previously held positions within R&D at Pharmacia and AstraZeneca.

He commented: “It will be very exciting and rewarding to develop Orexo's projects into innovative new drugs that can address significant medical needs.”

Sanofi’s prostate cancer drug Jevtana (cabazitaxel) has not been recommended by NICE in draft guidance in combination with prednisone or prednisolone as a second line treatment.

NICE’s Appraisal Committee raised concerns about the medication’s cost effectiveness, its associated adverse effects and evidence supplied by the manufacturer.

Sir Andrew Dillon, NICE Chief Executive, says that the Committee was “particularly concerned” about the uncertainty on patients’ renal and cardiac systems.

A number of factors are taken into consideration by NICE’s Appraisal Committees when assessing the cost effectiveness of a treatment. These include the medication’s clinical effectiveness, its side effects, the benefits it brings to patients and the financial cost.

This formula then enables them to determine the cost of using the drug to provide a year of the best quality of life available or quality adjusted life year (QALY). NICE says they usually recommend treatments that cost around £30,000 per QALY or less, however the cost of Jevtana was far greater than this figure.

“The manufacturer of cabazitaxel provided one study on the effectiveness of the drug; in this study cabazitaxel was shown to extend life by approximately 10 weeks,” said Sir Andrew. “Although cabazitaxel has been shown to be effective, it is also associated with a number of adverse events.”

He added that the Appraisal Committee was also concerned about the “validity” of the health related information supplied by Sanofi after it provided one study which demonstrated a median overall survival gain of 2.4 months and an mean overall survival gain of 4.2 in its model.

“The Committee also felt that the treatment did not meet the criteria to be considered under NICE’s special arrangements for end of life, as based on the current data the length of the life extension could not be considered robustly proven to be at least three months,” added the Chief Executive.

“Once all these factors had been taken into account it was estimated that the cost per QALY would be more than £89,000. Therefore the committee concluded that cabazitaxel would not be a cost effective use of limited NHS resources.”

If a drug does meet the criteria to be considered under the Institute’s supplementary advice for end of life treatments, a higher cost per QALY may be accepted by NICE. There is currently no set threshold cost per QALY that meets this criterion, but since the supplementary advice was introduced, the only drug recommended under this method has been Sunitinib for renal cell carcinoma at a cost of £50,000.

NICE said that Javtana did not meet this criterion because the Committee did not consider the length of the life extension to be “sufficiently robust”.

The diversity of wounds and the wounded means that the evidence base for wound care therapies is a complex issue. Professor Richard White of the University of Worcester and Wound Care Alliance UK looks at how companies can best establish the case for their products.

The current situation regarding issues of product evidence and product availability in wound care has been discussed in Medtech Business (May and June 2010). Therapies affected by these issues include silver and other modern wound treatments, such as moist wound healing dressings and topical negative pressure (TNP) devices, which have attracted the scrutiny of those who conduct systematic evidence reviews. Following those commentaries, this article offers some proposals for a way forward.

Therapies on trial

The modern age in wound care, dating from around 1970, has seen a variety of new medical devices come to market – many of which have achieved ‘standard of care’ status. For example, elastic and non-elastic compression bandaging; hydrocolloid, alginate, foam and film dressings; honey as a CE Marked product and many others have become established in the clinical armamentarium.

Countless clinicians, many of them acknowledged experts, have come to rely on these products, knowing that when they are correctly used they work well. This steady supply of products has come from an innovative, dynamic industry that works closely with the clinician.

However, the evidence gathered to support these products does not satisfy the various groups who insist on the Cochrane-style analysis of randomised clinical trials (RCTs). Recent publications have criticised the evidence for moist wound healing, antiseptic dressings and TNP. This criticism, published in the medical literature and the national press, has led to restrictions on product availability.

The key priority, in my view, should be to maintain a regular flow of safe and effective innovations, supported by sufficient evidence for regulatory purposes and for informing the clinician. The introduction of such products should, of necessity, be followed by the ongoing collection and publication of clinical evidence.

Innovation is vital to wound care, as the steady flow of new and improved products leads directly to better patient care. The discipline is still in its infancy – a stage when developments are frequent. The industry is populated by a broad mix of large, established companies and smaller companies, many of them start-up ventures. This affects the level of investment available for expensive RCTs.

Should trials be left to the wealthy companies alone? Or can other, more economical forms of clinical evidence be gathered instead? That would offer the smaller, less affluent companies greater opportunity to develop products, gather evidence and take their treatments to market – and in the past, that has been a significant feature of wound care in the UK.

There is no doubt that evidence in one form or another is essential for the development of wound care – so open discussion of the issues around what makes for effective evidence is needed. In addition, some proactive action on the part of the wound care sector is also essential: companies must, to my mind, take action before further restrictions in product availability are foisted upon them.

Finding the facts

There is a strong case for looking more carefully at what evidence is already available in the public domain. Cochrane analyses have been justly criticised for not taking all of the available evidence into consideration. A preferable method of analysis, with recommendations, is the GRADE system. This well-known and respected system, in my opinion, should be employed to assess the evidence for a number of existing products.

With regard to the ‘quality’ of different types of evidence, the European Wound Management Association (EWMA) has published guidelines for the conduct of RCTs in the May 2011 issue of the Journal of Wound Care.

If a company decides that an RCT is the most appropriate means of gathering clinical evidence, it is important that they avoid the pitfalls which have blighted many previous trials. The Cochrane reviews list the numerous shortcomings in trials, mainly methodological errors, which form grounds for disqualification. These can be avoided!

• At the planning stage, trials should be configured with purchasers in mind: as well as gathering clinical information, the trial should take account of economic factors and quality of life instruments.
• Once the data are published, these should enhance the chances of product uptake or changes in clinical practice. Quality data will make counter-arguments difficult and merit publication in quality journals, and so garner support from opinion leaders.

Case studies are frequently used to provide support for products. However, it is an unfortunate fact that many, probably most, of these studies are of very little value. This is due to their planning and objectives, as well as the information provided. When case study posters and journal reports make products appear to be panaceas, it is no wonder that the whole exercise becomes devalued.

Cohort studies, when properly conducted, can be valuable in many ways. Their merit has been extolled by many influential figures. The GRADE system of analysis gives reasonable weighting to such studies, whereas Cochrane analyses ignore them completely. Their format is less clear than that of RCTs – but when they are conducted in a multicentre setting, with clear objectives and endpoints such as clinical goals, economic factors and quality of life issues, they provide useful data.

Post-marketing surveillance studies, conducted long-term in the ‘real world’ of routine clinical practice, are under-used and under-estimated in wound care. As far as I am aware, they are mandatory in Germany and some quality data have been published from these studies.

Audit of clinical practice is as ‘real world’ as we can get when it comes to clinical (and hopefully financial) data. Efficient clinical settings can audit their practice for long-term outcomes in treatment of wounds. Such studies can provide the most meaningful evidence.

Value and cost

Cost-effectiveness, or health economics, has been a high priority in healthcare for many years, yet it does not figure in enough wound studies. Rather naively, claims of ‘cost-effective’ based on the unit price of a product still appear.

Health economics is a defined and refined science and must be recognised, and used, as such. In this respect there is vast room for improvement in company-sponsored wound treatment studies.

For the future, it is important that the evidence for wound care therapies is of better quality than it generally has been over recent decades. This is achievable through awareness of the literature and close liaison with experts – it does not necessarily need to incur substantially greater costs!

The whole dynamic of selling has changed over the past twenty years. No longer is it sufficient to demonstrate the product to a nurse or doctor and wait for the orders to flow in. Other key groups are now involved, and liaison with them to facilitate product uptake has become essential.

Everyone involved in wound care in the UK must now be aware of, and recognise the important role of, pharmacists, medicines management, formulary committees etc. Companies must do more to involve these groups.

The transition or evolution of standards for medical devices from the days of the first modern ‘moist wound dressings’ is remarkable. Following the enactment of the Medical Device Directives in the mid-1990s, the system has become more ordered and bureaucratic.

However, this process is far from complete. The recent furore over failing hip implants has shown that the current regulations are not adequate to prevent major clinical catastrophes involving medical devices. In the USA, the FDA is taking a very close look at device regulation.

As the standards for evidence become more sophisticated, better reflecting the realities of clinical practice, the medical device industry – and in particular, the sector supplying wound dressings and associated products – has the opportunity to address the need for change and adapt accordingly.

 

 

Richard White is Professor of Tissue Viability at the University of Worcester.

GSK’s Benlysta (belimumab) has not been recommended in draft guidance for treating systemic lupus erythematosus (SLE).

Questions were raised by NICE’s independent Appraisal Committee over concerns about the medication’s cost and clinical effectiveness against standard treatment options.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, says evidence “did not persuade the Committee that belimumab was good value for money”.

A Patient Access Scheme had been agreed between GSK and the DH for the treatment, although details of the agreement have been kept confidential at the request of Glaxo.

SLE is an incurable autoimmune condition, which mainly affects women. There are believed to be around 15,000 people in England and Wales with SLE, nine-out-of-ten are female.

The whole body is affected by SLE as the immune system attacks healthy parts of tissue and organs which may lead to serious internal damage.

It is a complex, poorly-understood condition and may be difficult to diagnose as symptoms are often similar to more common conditions.

“Systemic lupus erythematosus (SLE) is a debilitating condition which severely affects an individual’s quality of life,” said Professor Longson. “NICE’s independent appraisal committee has looked very carefully at the evidence provided on the use of belimumab for treating SLE, including the views of people with the condition, those who represent them, and clinical specialists.”

Although it is not licensed, certain patients with severe cases of the disease are treated with MabThera (rituximab). The Committee considered it relevant to compare Benlysta with MabThera, however NICE says there is no reliable data to show the relative efficacy between the two.

“Whilst recognising the severity of the disease, the Committee concluded that based on this evidence, belimumab could not be considered a good use of NHS resources,” added Professor Longson.

The decision is now open for consultation.

Eli Lilly has launched a new open innovation platform to develop its product pipeline as well as identify molecules to treat multi-drug resistant tuberculosis (MDR-TB).

The new Open Innovation Drug Discovery platform builds on Lilly’s Phenotypic Drug Discovery Initiative (PD²) that was launched in 2009 to identify molecules for future drug development.

Dr Jan Lundberg, Executive Vice President of Science and Technology and President of Lilly Research Laboratories, said: “We recognise that there are many untapped sources of ideas and molecules outside of Lilly that would otherwise go unnoticed without initiatives like this one that advance science."

The new platform consists of three components:

• TD², or target drug discovery, screens submitted molecules for their potential to interact with known disease targets.
• PD², which continues to screen submitted molecules in complex cellular assays with the goal of identifying potential medicines.
• A new initiative that screens molecules for their potential to fight against MDR-TB, a form of TB that resists against at least two first-line TB medicines.

Lilly has acknowledged that many reasons stifle the discovery process of new molecules, such as lack of resources, so has designed the new platform to minimise obstacles and benefit continued research.

The Open Innovation Drug Discovery platform utilises a secure website that enables scientists to submit molecules to be tested. A series of biological assay panels evaluate the molecule for its uniqueness and potential to be further optimised into a medicine candidate.

Dr Alan D. Palkowitz, Vice President of Discovery Chemistry Research and Technologies at Lilly, said that the new platform will “connect scientists from all over the world with Lilly, for the common goal of finding new treatments for diseases where patients are in need and looking for answers, such as cancer, diabetes and MDR-TB.”

The CHMP has recommended Astellas Pharma and Optimer Pharmaceuticals’ Dificlir (fidaxomicin) to treat adults with colon disease.

The drug specifically targets the bacteria causing the infection in the colon whilst avoiding ‘friendly’ bacteria in the gut of patients with the disease, which is also known as Clostridium difficile-associated diarrhoea (CDAD).

Ken Jones, President and CEO of Astellas Pharma Europe, said: “European patients with this potentially fatal disease can take encouragement from the positive CHMP opinion for Dificlir that a new medication for clostridium difficile infection may soon be available.”

Dificlir’s active substance is fidaxomicin, which belongs to the macrocyclic class of antibacterials and inhibits RNA synthesis by bacterial RNA polymerase.

Dr Xavier Luria, Head of Safety and Efficacy at the EMA, said: “This is a promising step forward in the Agency's drive for addressing patients' needs in infectious diseases.”

The positive opinion is based on Phase III clinical research data comparing fidaxomicin with oral vancomycin on patients in the US and Canada. Results of the studies showed that clinical cure was achieved at the end of ten days of treatment with both treatments. Furthermore, fidaxomicin had a significantly lower rate of recurrence of CDI compared to vancomycin.

Dificlir, known as Dificid in the US, was approved by the FDA in May for the treatment of CDAD in adults.

The European Commission will deliver its final decision within three months.

CDI is a serious illness resulting from infection of the internal lining of the colon by C. difficile bacteria. The bacteria produce toxins that cause inflammation of the colon, diarrhoea and, in some cases, death.

UK-based Astellas Pharma Europe manufactures and distributes pharmaceuticals globally with the intention to improve lives through the introduction of innovative and reliable pharmaceutical products.

Optimer Pharmaceuticals, is a biopharmaceutical company focused on developing and commercialising hospital specialty products to treat serious infections and address unmet medical needs.

Eli Lilly has received a positive opinion from the CHMP for Alimta as continuation maintenance therapy of advanced nonsquamous non-small cell lung cancer (NSCLC).

The recommendation is for the pemetrexed injection to be used as part of maintenance therapy, a relatively new concept in lung cancer treatment to commence immediately after patients have completed first-line treatment, in an effort to sustain disease control.

Dr Allen Melemed, Senior Medical Director of Alimta at Lilly Oncology, said: “Lung cancer is one of the most difficult cancers to treat and new therapy options are much needed.”

The CHMP’s recommendation will be reviewed by the European Commission, which will decide whether to approve the treatment for indication in Europe.

Dr Melemed commented: “If approved, Alimta would be the first tailored treatment option based on efficacy that can potentially extend lives beginning in first-line treatment and continuing through maintenance in advanced nonsquamous non-small cell lung cancer.”

No chemotherapy is currently approved as ‘continuation maintenance’ treatment. Currently approved lung cancer maintenance therapies use different medicines in the first-line and maintenance phases of treatment.

The CHMP's opinion was based on clinical research results from Paramount, a randomised, double-blind Phase III study involving patients with advanced nonsquamous NSCLC. Participants received initial therapy with four cycles of Alimta plus cisplatin. Patients whose disease did not progress continued to the maintenance phase, where survival was assessed in patients who received Alimta plus best supportive care (BSC), compared with those who received a placebo plus BSC.

Alimta is already approved in the first-line, maintenance and second-line settings in the EU and US for the indication. The treatment was originally recommended by NICE in September 2009 to treat the cancer on the NHS in the UK, but reversed its decision in December 2009, citing data uncertainties. NICE came to a final recommendation in June 2010.

Lung cancer is the most common form of cancer in the world, causing 1.3 million cancer deaths each year. NSCLC contributes to 85-90% of all lung cancers.