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Azilect Offers New Hope to Levodopa Treated Patients with Moderate to Advanced Parkinson's Disease

Benefits of Azilect seen when given alone or on top of concomitant dopamine agonist therapy

ATHENS, GREECE -- September 20, 2005 -- New data presented today in an oral presentation session, at the 9th congress of the European Federation of Neurological Societies, showed that treatment with Azilect (rasagiline 1 mg) once daily can provide significant additional benefits to levodopa treated patients with moderate to advanced Parkinson's disease (PD). These benefits were seen regardless of whether patients were receiving additional, optimized treatment with a dopamine agonist.¹

The new sub-analysis of the LARGO trial (Lasting effect in Adjunct therapy with Rasagiline Given Once daily), found that giving Azilect to patients already optimized on levodopa, with or without concomitant dopamine agonist (DA) treatment, significantly reduced daily "OFF" time (when the effects of medication wear off and PD symptoms return) by an average of 1.2 hours when compared to placebo, resulting in a clinically meaningful improvement in daily function for patients, without a related increase in dopaminergic adverse events.

Patients experienced a corresponding increase in "ON" time (when medication is working) without troublesome dyskinesias, the involuntary movements characteristic of long-term PD therapy.

Principle investigator, Professor Olivier Rascol, of University Hospital Toulouse, France, commented: "These data show that people with Parkinson's disease can achieve additional symptom benefits with Azilect, even when already receiving optimized levodopa treatment and irrespective of whether they are also receiving a dopamine agonist."

The significant improvements in functioning demonstrated by Azilect, on top of DA treatment, were also shown with all additional end points, such as Clinical Global Impressions measures during "ON" time, UPDRS-motor during "ON" time (symptoms of tremor, slowness of movement, stability and rigidity), and UPDRS-Activities of Daily Living scores during "OFF" time, (measuring the ability of patients to walk, speak, swallow, dress and get out of bed.)

The active comparator in the study, entacapone, demonstrated comparable reductions in daily "OFF" time, but results for some of the additional measures mentioned above did not achieve significance.

The LARGO study investigated the response to treatment in 687 levodopa treated patients who were randomized to receive Azilect, entacapone or placebo. Two thirds of patients in each arm were also receiving DA therapy, allowing for comparison of the effectiveness of Azilect given alone or on top of a dopamine agonist.¹

These data from the LARGO study add to the growing body of evidence for Azilect as an effective and well-tolerated treatment for Parkinson's disease. The findings from LARGO are consistent with the recently published study PRESTO, which also demonstrated that once daily Azilect, as an adjunctive therapy, significantly increases daily "ON" time and improves the cardinal symptoms of Parkinson's disease.²

In addition, data from the TEMPO trial, a study of Azilect as monotherapy, demonstrated that Azilect is an effective and well-tolerated treatment in early disease and can significantly delay the progression of PD symptoms.^3,4

About Azilect
Azilect is a novel, potent, second-generation, selective, irreversible monoamine oxidase type-B (MAO-B) inhibitor that blocks the breakdown of dopamine, a neurotransmitter that is critical for the regulation and coordination of movement. Azilect received approval from the EMEA in February 2005 as both a monotherapy and an adjunct therapy for Parkinson's disease, and is marketed in Europe by Lundbeck and Teva as part of a long-term strategic alliance between the two companies.

About Parkinson's Disease
Parkinson's disease (PD) is a progressive neurodegenerative, chronic disruption of the central nervous system. Symptoms include tremor, slowness of movement, stiffness, gait and posture problems.

As the disease progresses, symptoms worsen and the patient is likely to experience motor complications, including a fluctuating response to treatment.
During "ON" states, medication works effectively, but during "OFF" states, which correspond to the medication wearing off between doses, patients experience relatively poor function and mobility.

PD affects men and women equally, and an estimated four million people worldwide are affected by the disease, which typically occurs at a late age. Approximately 1.6% of the population over the age of 65 suffer from PD. It is estimated that well over one million people in the EU suffer from PD. In 2003, the worldwide market for PD drugs was valued at USD 2.5 billion with approximately 40% of this in Europe.

Dopaminergic adverse events are often seen with levodopa and dopamine agonist treatment and include sudden daytime sleepiness, hypotension, vomiting, diarrhoea, constipation and hallucinations.⁵

LARGO:
The LARGO trial was published in March 2005 in The Lancet. Findings showed that additional Azilect treatment significantly improves PD symptoms when compared with placebo in patients optimised on levodopa and concomitant PD medications. Azilect also demonstrated significant improvement compared to entacapone in gait, postural instability and "freezing" (when walking) – symptoms that are generally considered poorly responsive to levodopa therapy.⁵

Global scales used to measure Parkinson's disease symptoms include:
· UPDRS – The Unified Parkinson's Disease Rating Scale, a research tool commonly used to measure a patient's ability to perform mental and motor tasks and activities of daily life
· CGI – the Clinical Global Impressions scale, a global measure of function improvement.

References
1. Rascol O, Brooks, DJ, Melamed E, et al. Rasagiline is effective and well tolerated in the treatment of moderate to advanced Parkinson's disease patients receiving concomitant dopamine agonist therapy. Oral presentation presented at EFNS, September 17-20, 2005
2. Schwid S, Shoulson I, et al for the Parkinson Study Group. A Randomized Placebo Controlled Trial of Rasagiline in Parkinson's Disease Patients with Levodopa-Related Motor Fluctuations (The PRESTO Study). Arch Neurol 2005 Feb;62:241-248
3. Siderowf A, Stern M et al for the Parkinson Study Group. A Controlled Trial of Rasagiline in Early Parkinson' Disease (The TEMPO study). Arch Neurol 2002 Dec;59(12):1937-43
4. Parkinson Study Group. A Controlled, Randomised, Delayed-Start Study of Rasagiline in Early Parkinson disease. Arch Neurol 2004 Apr; 61:561-566
5. Rascol O, Brooks DJ, Melamed E, et al. Rasagiline as an adjunct to levodopa inpatients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. The Lancet 2005 March; 365:947-365


SOURCE: H. Lundbeck A/S and Teva Pharmaceutical Industries Ltd.

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