The First and Only Medicine for Parkinson's Disease Dementia is Now Available

FRIMLEY, England, May 24 /PRNewswire/ --

Exelon(R) (rivastigmine), the first and only medicine licenced for the treatment of mild to moderately severe dementia associated with idiopathic Parkinson's disease (PD) is now available.

Rivastigmine, already indicated for mild to moderately severe Alzheimer's disease (AD), is now the only medicine to be licensed for the treatment of Parkinson's disease dementia (PDD). Parkinson's disease is not merely a movement disorder. There are approximately 120,000 people with Parkinson's disease in the UK[1,2] and at any one time, up to 40% of these patients will suffer from varying levels of dementia[3,4]. It is one of the most distressing complications of PD for both patients and carers[5,6,7]. Patients experience a wide range of symptoms, the most troublesome of which are often behavioural, such as hallucinations, anxiety, apathy and depression and it is these symptoms which often result in a patient having to go into a nursing home[2,7].

"This is extremely encouraging news for patients affected by Parkinson's disease who then develop dementia," said Dr Jane Byrne, Senior Lecturer at the University of Manchester and Honorary Consultant in Old Age Psychiatry at the Wythenshawe Hospital, Manchester. "For many patients with Parkinson's disease, the dementia symptoms cause more distress for them and their carers than the physical symptoms. Now for the first time, there is a treatment proven to be clinically effective in some patients available for us to use."

"Dementia associated with Parkinson's disease is a significant problem for patients and their families. It often results in a major emotional and social burden and can lead to additional costs of care," said Robert Meadowcroft, Director of Policy, Campaigns and Information for the Parkinson's Disease Society, London. "We therefore welcome therapies like Exelon which give new hope to families caring for a loved one with dementia and may improve the quality of life of the whole family."

The approval is based on the outcome of a 24-week, randomised, multicentre, double-blind, placebo-controlled study (known as the EXPRESS study) involving 541 patients, including 52 patients from 9 different centres in the UK[8]. The results showed significantly positive outcomes for rivastigmine in all primary and secondary endpoints, i.e., that rivastigmine is efficacious on a wide range of symptoms of PDD and benefits were maintained over 48 weeks[8,9].

Rivastigmine is widely used to treat mild to moderately severe Alzheimer's disease (AD) and is included in the new Appraisal Consultation Document (ACD) from the National Institute for Health and Clinical Excellence (NICE) on the use of drugs to treat AD[10]. The ACD recommends the use of rivastigmine, along with other drugs in the class, in patients with moderate to moderately severe Alzheimer's disease, and that therapy should be initiated with the drug with the lowest acquisition cost. By NICE's own analyses, rivastigmine has been shown to be the most cost-effective drug for the treatment of AD, in addition to being the lowest cost drug in the class[10]. The Final Appraisal Document (FAD) is expected at the end of May.

Notes for Editor

About rivastigmine (Exelon)

- Rivastigmine is indicated for the symptomatic treatment for mild to moderately severe Alzheimer's dementia and for the symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson's disease. It belongs to a class of drugs

- known as cholinesterase inhibitors (ChEIs) which increase neurotransmitter activity in the brain[11]. Among the widely used ChEI's, rivastigmine is the only treatment that inhibits both enzymes involved in the breakdown of this neurotransmitter - acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In AD rivastigmine can maintain both memory and thinking and help patients cope better with the activities of daily living. It may help improve communication, social interaction, participation in hobbies and may enable them to eat and dress independently[12,13]. Rivastigmine was approved for the treatment of AD in 1997 and is currently used in over 70 countries with over 2.8 million patient years of treatment.

About Parkinson's disease, Parkinson's disease dementia, Alzheimer's disease and dementia

- Parkinson's disease (PD) is a chronic and progressive neurological condition estimated to affect 6.3 million people worldwide and approximately 120,000 in the UK[3,4]. Parkinson's disease is characterised by motor symptoms such as tremor, rigidity, shuffling gait and paucity of movement.

- Parkinson's disease dementia (PDD) - Dementia occurs in around 40 percent of patients diagnosed with PD[1,2] which equates to approximately 48,000 patients in the UK, although in one study following patients for 8 years it was shown ultimately to affect up to 80 percent of patients[14]. Parkinson's patients have a six-fold increase in the risk of developing dementia compared with elderly people without Parkinson's disease[15]

- Like Alzheimer's disease, dementia associated with Parkinson's disease is thought to result from a cholinergic deficit, which causes decreased transmission of signals between nerves in the brain, especially those that rely on the neurotransmitter acetylcholine. This deficit contributes to the cognitive and behavioural problems observed in these patients. Patients with dementia associated with Parkinson's disease typically have problems with memory, concentration, activities of daily living, as well as depression, anxiety, apathy and hallucinations[2].

- Alzheimer's disease (AD) is a progressive, degenerative disease that alters the brain, causing impaired memory, thinking and behaviour. Affecting over 750,000 people in the UK and approximately 10 million people worldwide, it is the most common form of dementia[16].

- Dementia occurs in different forms such as Alzheimer's disease, vascular dementia, dementia associated with Parkinson's disease, dementia with Lewy bodies, and is currently estimated to affect nearly 18 million people worldwide[16]. As the mean age of the population rises, this number is steadily increasing.

- The Parkinson's Disease Society runs a free phone national helpline - 0808-800-0303 - that provides advice and information to all people affected by Parkinson's. The hours of operation are Monday - Friday 09:30 - 21:00 and Saturdays 09:30 - 17:30.

The EXPRESS study

The EXelon in PaRkinson's disEaSe dementia Study (EXPRESS)8 is the first international multicentre, double-blind, placebo-controlled, study to demonstrate the efficacy and safety of any drug in the treatment of PDD. A total of 541 patients were studied including 52 from 9 different centres from the UK. The study was published in December 2004 in the New England Journal of Medicine[8].

The study shows that rivastigmine provides statistically and clinically significant benefits in dementia associated with Parkinson's disease. Patients treated with rivastigmine improved across a wide range of symptoms. They demonstrated improvements in memory, concentration and behavioural problems and were also better able to cope with everyday activities.

Over a 24-week study period, patients were randomly assigned to a daily dose of 3-12 mg rivastigmine or placebo. Investigators used two measures regularly applied in clinical studies of patients with dementia: the Alzheimer's disease Assessment Scale (ADAS-cog) to evaluate patients' cognitive function; and the Alzheimer's disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC) to assess the patients' overall functioning. Patients who were treated with rivastigmine showed a mean 2.1-point improvement (versus a 0.7-point decline in placebo) on the ADAS-cog scores (p< 0.001) at week 24 of the study. Mean ratings on the ADCS-CGIC were 3.8 on rivastigmine versus [4.3] on placebo (p= 0.007) (N.B. the lower the score the better the effect). Additional specific tests for memory, attention, behavioural symptoms and verbal fluency consistently showed significantly better outcomes for rivastigmine versus placebo (all p< 0.05).

The most common side effects in this study were nausea and vomiting, which are common side effects of cholinesterase inhibitors. Importantly, motor scale assessments showed that Parkinsonian symptoms were not worsened overall relative to baseline or placebo. Mild to moderate tremor was reported in rivastigmine-treated patients, but this rarely resulted in withdrawal from the study.

UK EXPRESS Centres

In the UK, 9 centres took part in the study:

- Cardiff

- Newcastle

- Manchester

- Lewisham

- Royal Free Hospital, London

- St George's Hospital, London

- Blackpool

- Liverpool

- Hastings

About Novartis

Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2003, the Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 80 000 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

References:

1. European Parkinson's Disease Association, Global Declaration on Parkinson's Disease, 2003. http://epda.eu.com

2. Parkinson's Disease Society, Media Briefing Sheet. http://www.parkinsons.org.uk

3. Cummings JL. Intellectual impairment in Parkinson's disease: clinical, pathological and biochemical correlates. J Geriatr Psychiatry Neurol 1988;1:24-36.

4. Emre M. Dementia associated with Parkinson's Disease. Lancet Neurology 2003;2:229-37

5. Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson's Disease? J Neurol Neurosurg Psychiatry 2000;69:308-12.

6. Aarsland D, Larsen JP, Karlsen K, et al. Mental symptoms in Parkinson's disease are important contributors to caregiver distress. Int J Geriatric Psychiatry, 1999;14:866-74.

7. Aarsland D, Karlsen K. Neuropsychiatric aspects of Parkinson's disease. Curr Psychiatry Rep 1999; 1: 61-8.

8. Emre M et al. Rivastigmine for the dementia associated with Parkinson's Disease patients: a randomized double-blind, placebo-controlled study. N Eng J Med 2004; 351:29-38.

9. Poewe W et al. on behalf of the EXPRESS Investigators. Long term benefits of rivastigmine in dementia associated with Parkinson's disease: an active treatment extension study. Mov Disord 2006;21:456-61

10. NICE Appraisal Consultation Document www.nice.org.uk

11. Exelon SmPC Novartis Pharmacueticals

12. Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int J Geriatr Psychopharmacol 1998;1:55-65.

13. Rösler M, Anand R, Cicin-Sain A et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomized controlled trial. BMJ 1999;318:633-40

14. Aarsland D, Anderson K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003;60:387-92.

15. Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen P. Risk of dementia in Parkinson's disease: a community-based, prospective study. Neurology. 2001;56(6):730-6

16. Alzheimer's Society Policy Position Paper on Demography, July 2004