Landmark study in New England Journal of Medicine shows Exelon® may help people suffering from dementia associated with Parkinson's disease

Basel, Switzerland, December 9, 2004 - Exelon® (rivastigmine tartrate) can provide significant benefits in dementia associated with Parkinson's disease (PD) , according to a study published in the New England Journal of Medicine this month.

 

The study, known as EXPRESS (EXelon in PaRkinson's disEaSe dementia Study), is the first large-scale clinical trial assessing the efficacy and safety of an Alzheimer's disease treatment in PD patients with dementia.[1] Exelon has been widely used in Alzheimer's disease dementia since its approval in 1997.

 

Patients taking Exelon showed statistically significant benefits on a range of symptoms, such as loss of memory, concentration and behavioral problems. They were also able to cope better with everyday activities like watching TV or talking about current events.

 

"The findings of the EXPRESS study could have important implications for clinical practice," said Dr Murat Emre, Professor of Neurology at the Istanbul University in Turkey, lead investigator of the EXPRESS study.

 

"With current treatments we are able to manage the movement symptoms of Parkinson's disease quite well, but dementia has been an area which could not be treated up to now. Rivastigmine is a therapy that has been shown to improve symptoms frequently seen in patients suffering from dementia associated with PD and thus offers hope to provide a better quality of life," Dr. Emre said.

 

Dementia is one of the complications most feared by PD patients.[2]  In addition to cognitive impairment, neuro-psychiatric symptoms like depression, hallucinations, anxiety and apathy, are also common.[3]  These symptoms are important determinants of the patient's quality of life, course of the disease and caregiver distress.3 Two out of five people with PD develop dementia over the course of their illness.[4],[5] Patients with PD have a six-fold increase in the risk of developing dementia compared with elderly people without PD.

 

"Dementia associated with Parkinson's disease places a significant emotional, economic and social burden on patients and their families," said Mary Baker, President of the European Parkinson's Disease Association, which is based in the United Kingdom.

 

"As the person with PD becomes increasingly dependent, watching someone that you care for start to deteriorate in this way is heart breaking, and the future becomes an uncertain abyss for all the family. Sometimes institutional care is the only option and this places a significant economic burden on the family and the state. Results like this give new hope to families caring for a loved one with dementia and may improve the quality of life of the whole family," Baker said.

 

Over a 24-week study period, patients were randomly assigned to a daily dose of 3-12 mg Exelon or placebo. Investigators used two measures regularly applied in clinical studies of patients with dementia: the Alzheimer's Disease Assessment Scale-cognition (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 Exelon 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). Additional specific tests for memory, attention, behavioral symptoms and verbal fluency consistently showed significantly better outcomes for Exelon versus placebo (all p< 0.05). Since patients receiving placebo declined by nearly 1 point on the ADAS-cog over 24 weeks, an improvement of 2.1 points in the rivastigmine group might represent approximately one year's advantage.

 

The side effects associated with Exelon during this study were mild to moderate in nature and included nausea and vomiting. Importantly, motor scale assessments showed that Parkinsonian symptoms were not worsened overall relative to baseline or placebo. Mild to moderate tremor was reported in Exelon-treated patients, but this rarely resulted in withdrawal from the study. 

 

Exelon is a treatment for mild to moderate Alzheimer's disease. It belongs to a class of drugs known as cholinesterase inhibitors (ChEI's) which increase neurotransmitter activity in the brain. It was approved for the treatment of Alzheimer's disease in 1997 and is currently used in over 70 countries.

 

Among the widely used ChEI's, Exelon is the only treatment that inhibits both enzymes involved in the breakdown of the neurotransmitter acetylcholine - acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). This may offer additional benefits over treatments which inhibit AChE alone. Exelon can maintain both memory and thinking, help with behavioral problems and affect how patients cope with the activities of daily living. It may help them communicate better, interact socially, participate in hobbies and eat and dress independently.[6],[7]

 

Parkinson's disease (PD) is a chronic and progressive neurological condition estimated to affect 6.3 million people worldwide.[8] Dementia occurs in around 40 percent of patients diagnosed with PD and may affect up to 80 percent of Parkinson's patients as the disease further progresses.[3],[9]

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 behavioral 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.[5] ,[10]

Alzheimer's disease (AD) is a progressive, degenerative disease that alters the brain, causing impaired memory, thinking and behavior. Affecting approximately 10 million people worldwide and two to six percent of those over 65 years of age, it is the most common form of dementia and the third leading cause of death in this age group behind cardiovascular disease and cancer.[11]

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.[12] As the mean age of the population increases, this number is steadily increasing.

 

This release contains certain forward-looking statements relating to the Company's business, which can be identified by the use of forward-looking terminology such as   "provides significant benefits", "could", "offers hope to provide", "may improve", "might represent", "may offer", "may help", "is committed to addressing", or similar expressions, or by express or implied discussions  regarding potential new indications for Exelon, or regarding potential future revenue from Exelon. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Exelon to be materially different from any future results, performance or achievements expressed or implied by such statements.  There can be no guarantee that Exelon will be approved for any additional indications in any market or regarding potential future revenue from Exelon.  In particular, management's expectations regarding commercialization of Exelon could be affected by, among other things, additional analysis of Exelon clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays in government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures; as well as factors discussed in the Company's Form 20-F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected.  Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

 

Novartis has been a leader in the neuroscience area for more than 50 years, having pioneered early breakthrough treatments for Alzheimer's disease, Parkinson's disease, attention deficit/hyperactivity disorder, epilepsy, schizophrenia and migraine. Novartis continues to be active in the research and development of new compounds, is committed to addressing unmet medical needs and to supporting patients and their families affected by these disorders.

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 approximately 80,000 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.