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

9/1/2003, 7:30 AM (Source: GlobeNewswire)

Basel, 1 September 2003 - Results from new clinical studies with
Stalevo(TM) presented today at the 7th Congress of the European
Federation of Neurological Societies in Helsinki, Finland confirm
clear patient benefits. Data from these first-ever 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, its
long term utility is limited by the occurrence of motor
complications. Stalevo was therefore developed to optimize the
pharmacokinetic profile of levodopa and enhance its clinical

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 Stalevo7. These
first-ever clinical studies provide valuable data regarding dosing,
tolerability and efficacy of Stalevo.

Commenting on the clinical relevance of the TC-INIT study8, 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%
(investigator assessment) and 81% (patient assessment) of patients
reported improved symptom control versus 76% (investigator
assessment) and 73% (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.

Interim 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

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

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 US 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).

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 "first-ever studies" or similar
expressions, or by express or implied discussions regarding potential
future sales of Stalevo. Such forward-looking statements reflect the
current views of the Company regarding future events, and 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. There can be no guarantee that the aforementioned
clinical trials will result in the commercialization of Stalevo in
any market. Any such commercialization can be affected, among other
things, uncertainties relating to unexpected regulatory delays,
further clinical trial results, the ability to obtain or maintain
patent or other proprietary intellectual property protection,
government regulation or competition in general, increased government
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.

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

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 78 200
people and operate in over 140 countries around the world. For
further information please consult

Notes to Editor:
o Parkinson's disease (PD) is a chronic and progressive
neurological condition. 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 years12.
o 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.
o 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
optimized 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.
o Randomized, 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 50mg, 100mg and 150mg
with corresponding doses of levodopa/carbidopa and entacapone and
served as the basis for approval by regulatory agencies.

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:
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:
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
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

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