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First results of three multicenter open-label clinical trials with StalevoTM show improved symptomatic benefits and enhanced convenience for patients with Parkinson's disease.

Helsinki, 1 September 2003
- Results from new clinical studies with Stalevo presented today at the 7th Congress of the European Federation of Neurological Societies in Helsinki, Finland confirm clear patient benefits. Data from these firstever studies in patients with Parkinson's disease (PD) taking Stalevo - the new levodopa combination product containing levodopa, carbidopa and entacapone - show enhanced symptomatic benefits resulting in greater control of PD symptoms, as well as convenience of administration compared to traditional levodopa therapy.
 
While levodopa therapy remains the cornerstone of PD treatment, it's long term utility is limited by the occurrence of motor complications. Stalevo was therefore developed to optimise the pharmacokinetic profile of levodopa and enhance its clinical benefits.
 
The individual components of Stalevo have a well-established efficacy record supported by numerous clinical trials1,2,3,4,5,6, which provided the basis for regulatory agency approval of Stalevo.7 These first-ever clinical studies provide valuable data regarding dosing, tolerability and efficacy of Stalevo.
 
Commenting on the clinical relevance of the TC-INIT study,8 one of the lead investigators, Professor David Brooks, of the Medical Research Council Clinical Sciences Centre and Imperial College London, UK said: "These interim data show that levodopa treated PD patients may be switched to Stalevo and experience enhanced benefits of their levodopa therapy. In addition, this real-life experience is significant as it demonstrates that the switch can be achieved easily and conveniently".
 
The TC-INIT study compares the switch from traditional levodopa/dopa decarboxylase inhibitor (DDCI) therapy to either Stalevo or levodopa/DDCI plus entacapone (Comtess/Comtan) tablets taken separately in 200 PD patients experiencing wearing-off symptoms. Interim results of 111 patients show that patients taking Stalevo experience improved symptom control comparable to levodopa/DDCI plus entacapone taken separately. At the end of week two, a majority of patients saw their condition improve when their levodopa therapy was optimized. When switched to Stalevo, 82 percent (investigator assessment) and 81 percent (patient assessment) of patients reported improved symptom control versus 76 percent (investigator assessment) and 73 percent (patient assessment) when switched to levodopa/DDCI plus entacapone taken separately.
 
In addition, treatment with Stalevo as a single tablet was easy to initiate and provided simplicity and convenience of administration for patients.
 
Preliminary data from a second study (SELECT-TC) assessing the switch to Stalevo in 160 PD patients currently being treated with levodopa/carbidopa and experiencing wearing-off symptoms, indicate that the majority of patients can easily be transferred to Stalevo with few, or no levodopa dose adjustments.9
 
"These data show that dose modifications are rarely needed when switching from levodopa treatment to Stalevo and can be accomplished with ease and convenience, and most importantly with the patient's acceptance. There are a number of complicated regimens that currently exist in PD treatment. Many patients often have to take medications for other co-existing conditions. Stalevo clearly has everyday practical benefits for patients and for physicians prescribing the treatment by combining three medicines in one", added Professor David Brooks.
 
In a third, four-week completed study (SIMCOM) more than two-thirds of the patients preferred taking Stalevo to levodopa/DDCI and entacapone taken separately. Furthermore, the vast majority of patients reported that Stalevo was easier to dose, use, handle and swallow.10
 
In all studies, Stalevo was generally well tolerated. The most common side effects were dopaminergic in nature (e.g. dyskinesia or involuntary movements, nausea). These side effects are mild and moderate in nature, and when they occur, they can usually be managed with dose modifications. Side effects seldom lead to treatment discontinuation. In addition, the components of Stalevo have a well-established safety and tolerability profile supported by numerous clinical trials1,2,3,4,5,6 and over 300,000 patient years of experience with levodopa/DDCI plus entacapone.11
 
Novartis and Orion Pharma received U.S. Food and Drug Administration (FDA) approval for Stalevo in June 2003 and have recently [26 June 2003] received a positive opinion from the European Committee for Proprietary Medicinal Products (CPMP).
 
Notes to Editor:
-
Parkinson's disease (PD) is a chronic and progressive neurological conditio n. The overall prevalence of Parkinson's disease in the world is estimated to be 6.3 million. It affects 1 per 100 persons over the age of 60 years and 1 per 50 people over the age of 80 years.12
- The cornerstone of PD treatment is levodopa. It can provide benefit throughout the whole course of the disease and is the only medication that has been shown to have an effect on quality of life and significantly prolongs life expectancy in PD patients.13 However, when standard levodopa therapies are used over the long term, patients may begin to experience a wearing-off of its clinical effects, with changes in mobility, mood and sensation, and treatment may need to be adjusted periodically.
- Stalevo is the first new levodopa treatment in many years and combines levodopa, carbidopa and entacapone. Whilst carbidopa reduces the side effects of levodopa, entacapone enhances its benefits, offering smoother and more consistent plasma levels of levodopa. This optimised pharmacokinetic profile translates into significant improvement in the PD patient's ability to perform everyday tasks and alleviates motor complications associated with long-term therapy.
- Randomised, single-dose, four-way crossover studies investigating the pharmacokinetics of Stalevo in healthy subjects showed that Stalevo was bioequivalent to levodopa/carbidopa and entacapone administered separately without requiring dose modification.7 The studies evaluated the bioequivalence of Stalevo 50 mg, 100mg and 150 mg with corresponding doses of levodopa/carbidopa and entacapone and served as the basis for approval by regulatory agencies.
 
References:
1. Larsen JP, Worm-Petersen J, Siden A, Gordin A, Reinikainen K, Leinonen M and the NOMESAFE Study Group. The Tolerability and Efficacy of Entacapone Over Three Years in Patients with Parkinson's Disease. Eur J Neurol 2003, 10: 137-146.
2. Brooks D, Sagar H & the UK-Irish Entacapone Study Group. Entacapone is Beneficial in Both Fluctuating and Non-fluctating Patients with Parkinson's Disease. A Randomised, placebo-controlled, Double-blind, Six-month Study. J Neurol Neurosurg Psychiatry 2003; 74: 1064-1072.
3. Myllylä V, Kultalahti E, Haapaniemi H, Leinonen M, & the Filomen Study Group. Twelve-month Safety of Entacapone in Patients with Parkinson's Disease. Eur J Neurol 2001; 8:53-60.
4. Parkinson Study Group. Entacapone Improves Motor Fluctuations in LEVODOPA-Treated Parkinson's Disease Patients. Ann Neurol 1997; 42: 747-755.
5. Poewe W, Deuschl G, Gordin A, Kultalahti E, Leinonen M, & the Celomen Study Group. Efficacy and Safety of Entacapone in Parkinson's disease Patients with Suboptimal Levodopa Response : a 6-month Randomised Placebo-controlled Double-blind Study in Germany and Austrial (Celomen Study). Acta Neurol Scand 2002; 105: 245-255.
6. Rinne UK, Larsen JP, Siden Å, Worm-Petersen J, & the Nomecomt Study Group. Entacapone Enhances the Response to Levodopa in Parkinsonian Patients with Motor Fluctuations. Neurology 1998; 51: 1309-1314.
7. Heikkinen H, Varhe A, Lyly V, Korpela K, Laine T and Kaakkola S. New Triple Combination of Levodopa, Carbidopa and Entacapone for the Treatment of Parkinson's Disease. Presented at the 7h Congress of the European Federation of Neurological Societies, 31 August 2003, Helsinki, Finland.
8. Brooks D, Agid Y, Ostergaard K, Widner H and Oertel W. A New Triple Combination Tablet is Easy to Initiate and Provides Improved Symptom Control in Patients with Parkinson's Disease. Presented at the 7h Congress of the European Federation of Neurological Societies, 31 August 2003, Helsinki, Finland.
9. Koller W, Hubble J, Guarnieri M, McCague K. Switching to Entacapone /Levodopa /Carbidopa Combination Therapy - Tolerability in Clinical Practice. Presented at the ' Optimising Levodopa Therapy ' Novartis and Orion Pharma sponsored satellite symposium, 7th Congress of the European Federation of Neurological Societies, 31 August 2003, Helsinki, Finland.
10.Myllylä V, Kaakkola S, Miettinen T, Heikkinen H, Reinikainen K. New Triple Combination of Levodopa/Carbidopa/Entacapone is a Preferred Treatment in Patients with Parkinson's Disease. Presented at the 7h Congress of the European Federation of Neurological Societies, 31 August 2003, Helsinki, Finland.
11. Orion and Novartis data on file.
12. Parkinson's disease fact sheet, European Parkinson's Disease Association.
13.Rajput RH. Levodopa prolongs life expectancy and is non-toxic to substantia nigra.
Parkinsonism and Related Disorders, 2001 8: 95-100. Parkinsonian Relat Disord. 2001; 8(2):95-100
 
For more information please contact:
Cat Barnett on: +44 20 7309 1063
Andrew Pearce: +44 20 7309 1279
 
 
Forward Looking Statement
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 "mark the first time," "produces effects," "effective therapy," "major advance in treatment" "offers great potential" and "significantly increases" or similar expressions, or by discussions of strategy, plans or intentions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Stalevo to be materially different from any future results, performance or achievements expressed or implied by such statements. Some of these are uncertainties relating to unexpected regulatory delays, further clinical trial results regarding efficacy or safety of Stalevo, government regulation or competition in general, as well as factors discussed in the Company's Form 20F filed with the 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.
 
About Orion Pharma
Orion Pharma is a research and development-orientated pharmaceutical division of the Orion Group (HEX:ORIA, ORIB), which is one of the leading companies in the healthcare sector in the Nordic area of Europe. Pharmaceutical R&D at Orion Pharma focuses on three core therapy areas: CNS therapies, cardiology and critical care, and hormonal therapies. Entacapone, a COMT enzyme inhibitor used in the treatment of Parkinson's disease, is one of Orion Pharma's patented molecule discoveries. It is available globally as Comtess and Comtan. It is also one of the three active compounds in Orion's novel levodopa treatment, Stalevo, which is already approved in the US and awaiting European marketing approval. For further information please consult http://www.orionpharma.com/.
 
About Novartis
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 77 200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
 
 
BACKGROUNDER
PARKINSON'S DISEASE
 
Definition:
- Parkinson's disease (PD) is a chronic, progressive disorder of the central nervous system, which causes increasing disability over time. The condition is most characterised by resting tremor, muscular rigidity, stooped posture and slowness or difficulty in movement.
 
Signs & Symptoms:
- Parkinson's disease remains one of the most difficult disorders to diagnose because the symptoms are similar to those of other conditions and it is unlikely that any two patients will have the same symptoms or prognosis.
- While difficult to diagnose, there are four cardinal symptoms of PD. The most common and perhaps the best known is resting tremor, which is uncontrolled shaking, usually in the hands or feet and when the muscles are relaxed. Many patients also experience rigidity, or stiffness of the limbs; bradykinesia, noted by the slowness of movement; and postural instability or a difficulty with balance.
- In addition to these visible signs, many PD patients also experience neuropsychological effects of the disease including dementia, depression, memory loss, confusion and agitation.
 
Causes:
- Whilst researchers have identified the brain mechanism that results in PD, the exact cause of the disease remains unknown. What is clear is that individuals who have lost more than about 80 percent of their dopamine supply (produced mainly in the substantia nigra) tend to develop PD symptoms, as dopamine is pivotal to control movement by carrying messages from nerve cell to nerve cell in the brain.
 
Prevalence:
- Worldwide, the prevalence of PD is estimated to be 6.3 million. It affects 1 per 100 persons over the age of 60 years and 1 per 50 people over the age of 80 years1. The average person is 60 years old at the onset of the disease, although 15 percent of cases affect those under age 40.
 
Treatment regimen:
- While there is no cure at this time, major advances in Parkinson's treatment have occurred in recent years, based on new understandings of the condition and disease process. Early diagnosis, medications, rehabilitation strategies and self-help efforts have been shown to benefit PD patients and improve their quality of life.
 
Treatment:
- The cornerstone of treatment of PD is levodopa. Levodopa, also known as l-dopa is converted into dopamine in the brain. It can provide benefit throughout the whole course of the disease and is the only medication that has been shown to have an effect on quality of life and significantly prolongs life expectancy in PD patients2. However, patients may often begin to experience a wearing-off of its clinical effects, with changes in mobility, mood and sensation, and treatment may need to be adjusted periodically. A number of adjunctive PD medications are available for use with levodopa.
- A recent breakthrough is a new treatment called Stalevo. Stalevo is a new levodopa combination product that contains levodopa, the most widely used agent for Parkinson's disease, plus carbidopa and entacapone. It enhances the clinical benefits of levodopa - efficacy and control of PD symptoms- by providing smoother, extended levodopa levels.
- Stalevo has a favourable tolerability profile with limited adverse effects3,4,5.
- Stalevo is convenient and easy to administer, with three dosage strengths covering the needs of a majority of patients.
 
 
References:
1. Parkinson's disease fact sheet, EPDA.
2. Rajput RH. Levodopa prolongs life expectancy and is non-toxic to substantia nigra. Parkinsonism and Related Disorders, 2001 8: 95-100. Parkinsonian Relat Disord. 2001; 8(2):95-100
3. Brooks D, Agid Y, Ostergaard K, Widner H and Oertel W. A New Triple Combination Tablet is Easy to Initiate and Provides Improved Symptom Control in Patients with Parkinson's Disease.
Presented at the 7h Congress of the European Federation of Neurological Societies
, 31 August 2003, Helsinki, Finland.
4. Myllylä V, Kaakkola S, Miettinen T, Heikkinen H, Reinikainen K. New Triple Combination of Levodopa/Carbidopa/Entacapone is a Preferred Treatment in Patients with Parkinson's Disease.
Presented at the 7h Congress of the European Federation of Neurological Societies
, 31 August 2003, Helsinki, Finland.
5. Heikkinen H, Varhe A, Lyly V, Korpela K, Laine T and Kaakkola S. New Triple Combination of Levodopa, Carbidopa and Entacapone for the Treatment of Parkinson's Disease. Presented at the 7h Congress of the European Federation of Neurological Societies, 31 August 2003, Helsinki, Finland.