The Forgotten Patients

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For many years, the treatment and care of people with dementia suffered from medical impotence and society’s indifference. Now, this growing patient class is getting more attention. How is the revolution in dementia care affecting the UK market for Alzheimer’s disease drugs?

The word most often used to describe the care of people with Alzheimer’s disease (AD) and other forms of dementia in the UK is ‘shocking’. From official reports to newspaper headlines, the diagnosis, early-stage treatment and late-stage care of people increasingly unable to express themselves have repeatedly been found seriously inadequate. It has often been pointed out that the patients do not choose to forget, but their doctors, nurses and care workers sometimes do.

The problem is complex. AD was first described in 1906, and the misconception that ‘senility’ is a normal consequence of old age is still widespread. Because AD patients become progressively less able to make choices and express views, their power to influence their own care is limited. Partners and family members often find it easier to regard the patient’s condition as a kind of ‘death’ – and while such a view may be a way of coping with loss, for it to colour the mindset of health and care providers is unacceptable.

In terms of medication, AD presents further challenges. A neurodegenerative disease, AD is progressive and irreversible. There are drugs that can delay its progression (in the earlier or later stages) and temporarily moderate the symptoms, especially when combined with behavioural therapies. So far, that’s all that can be done. The use of antipsychotics to suppress disruptive behaviour in people with dementia is no longer accepted as a norm of treatment.

Public awareness of AD has benefited in recent years from the high-profile intervention of fantasy author Terry Pratchett, whose ‘Discworld’ novels are major bestsellers. Since being diagnosed with early-onset AD in his late fifties, Pratchett has worked to raise public awareness of the inadequacies of dementia care. A shocking (there’s that word again) fact is that he has had to pay privately for his own medication, as Aricept – which costs only £2.50 per day – is only approved by NICE for treatment of people aged 65 and over (an age Pratchett reaches on 28 April this year).

In an interview with Fiona Phillips, another campaigner for better AD care, Pratchett made the moving statement: “I think the best thing I ever did with my life was stand up and say I’ve got Alzheimer’s.” He noted that while people with cancer are recognised as having the right to immediate treatment, people with AD and their families are often “left to get on with it”. The NHS tries too hard to prolong life, he argued, but does not try hard enough to maintain quality of life.

Pratchett’s determination to challenge the stigma of AD and the under-achieving norms of care for people with the condition has certainly had an impact. But will future dementia treatment be able to prevent or cure AD – or is it, like the Discworld, doomed to a permanent ‘flat earth’ phase?

Quality of life

The dementia care revolution began with the Banerjee report (2009) into the over-use of antipsychotics in care homes and nursing homes to suppress disruptive behaviour in AD patients. Dr Sube Banerjee stated that about 145,000 people with dementia were being inappropriately treated with antipsychotic medication in the UK, and that these powerful drugs were causing around 1,800 deaths each year. He recommended that the number of patients given such treatment should be reduced by two-thirds.

The National Dementia Strategy ‘Living well with dementia’ (2009) outlined key objectives and outcomes to improve the diagnosis, treatment, care and support of people with dementia across the range of care locations and through the entire patient pathway. It sought to make dementia care more comparable, in terms of methods and expectations, to that of other life-limiting medical conditions, and to ensure that all roles within the care pathway were clearly defined.

In March 2012, Prime Minister David Cameron launched the ‘Dementia challenge’, calling for “an all-out fight back against dementia”. He noted that about 670,000 people were living with dementia in the UK, and the number was expected to double within 30 years. The challenge promised to make the provision of information for patients, carers and professionals about relevant local health and care services mandatory; and to double the public funding for research into dementia.

A year later, the DH launched a dementia nursing strategy that defined the skills and capabilities expected of general, “dementia skilled” and specialist nurses working across all care settings. Emphasis was placed on the need for “seamless” integrated care. Significantly for industry, the strategy requires nurses to be “research aware and committed to delivering evidence-based care”.

A four-card hand

These developments mean that the AD market is primed for effective medicines and strategies for optimising their use. What does pharma have to offer?

Four drugs are currently approved by NICE for treatment of AD: Aricept (donepezil) from Eisai, Reminyl (galantamine) from Shire, Exelon (rivastigmine) from Novartis and Ebixa (memantine) from Lundbeck.

The first three drugs are cholinesterase inhibitors: they inhibit the breakdown of acetylcholine, a neurotransmitter, thus compensating for the loss of neural transmission that occurs in AD. They are recommended for use in patients with mild to moderate AD (in a 2011 update to the original NICE guidance, which recommended them only for moderate AD). However, the patents on Aricept and Reminyl expired in 2012, while the Exelon patent was declared invalid by the Court of Appeal in January 2013 on the grounds that it was an “obvious” application.

Up to 70% of eligible patients benefit from receiving cholinesterase inhibitors, showing improvements in both cognitive and emotional health. In most cases, disease progression is delayed by only six to 12 months. Ebixa is the only drug recommended for use in patients with moderate to severe AD. Its action is linked specifically to the effects of AD: it blocks the chemical glutamate, which is produced excessively by damaged brain cells and triggers a cascade of further cell damage. Ebixa can help patients to maintain everyday function, and may also reduce anxiety.

Lundbeck’s patent for Ebixa expires in April 2014. The company has supported NHS organisations to review dementia patients and reduce the inappropriate use of antipsychotics such as risperidone – which are clinically appropriate only for a minority of patients with moderate to severe AD, and are associated with increased risks of falling and infection. Painkillers, which can be used safely as an adjunct to anti-dementia drugs, can also reduce behavioural symptoms.

Better medicines use

Two challenges face the pharmaceutical industry in relation to AD treatment. Firstly, can it work with healthcare providers to optimise medicines use in the context of integrated care? Secondly, can it develop drugs that go further in preventing and treating AD than those currently available?

One company that has been active in medicines optimisation is Lundbeck, mental health specialist and manufacturer of Ebixa. As part of its partnership strategy, Lundbeck UK has supported a number of organisations in improving dementia care. The clarity of the 2011 NICE guidance on the use of AD drugs has made it easier for Lundbeck to work with the NHS in this disease area.

For example, Lundbeck’s project with NHS Sandwell (now replaced by Sandwell and West Birmingham CCG) used an Integrated Performance Framework to drive change in clinical practice. The project, which was described in an HSP Partnership in Practice supplement in 2012, had two goals: to build on the existing mapping and reduction of inappropriate prescribing of antipsychotics in care homes; and to help develop a local tool to support care home staff and enable GPs and psychiatrists to work together more.

NHS Sandwell, Lundbeck and performance consultancy Res Consortium formed a working group together with local health and care stakeholders. The project focused on AD patients with behavioural symptoms referred to locally as ‘Distress Reactions’, who were likely to be on antipsychotics and to need emergency admissions. Lisa Hill, Senior Commissioning Manager for mental health at Sandwell PCT, described the project as “a positive piece of integrated working resulting in a clear pathway and developing clinical leadership to address a complex issue”.

A brighter future

As with cancer, the targeting of disease mechanisms at the cellular level promises to deliver more effective AD treatments. The pipeline includes therapies based on two novel targets: Lundbeck and Otsuka have formed a partnership to develop and license a selective 5HT6 receptor agonist for use as an adjunct to donepezil; and a new UK biotech company, CoCo Therapeutics, has formed to develop new AD drugs targeting the retinoic acid receptor gene.

Dr Simon Ridley, Head of Research at the charity Alzheimer’s Research UK, commented: “A treatment that could stop the disease in its tracks would be a ‘holy grail’ for Alzheimer’s researchers.

“Much of the current efforts to develop new drugs for Alzheimer’s are focused on a protein called amyloid, which builds in the brains of people with the disease. Drugs designed to target amyloid have not yet shown benefits for patients in clinical trials, but it may be that these trials were carried out too late in the disease process.

“We now know that amyloid build-up occurs years before symptoms first appear, and many researchers believe that drugs targeting amyloid will need to be given early.

“Work to uncover potential new treatment targets must also continue,” Dr Ridley added. “To make the fastest progress, it’s vital to keep researchers talking to each other, which is why at Alzheimer’s Research UK we are working to connect our scientific teams with the pharmaceutical industry.”