FOR THE ATTENTION OF ACCREDITED MEDICAL WRITERS ONLY
Data presented at major international congress
Additional five-year open-label data provided evidence for long-term safety and efficacy of Neupro® (rotigotine) in Restless Legs Syndrome (RLS)
Brussels (Belgium), 18 June 2010, 1430 CET - The first data to show that Neupro® (rotigotine) significantly improved wellbeing and daily activities that are often impaired by pain related to Restless Legs Syndrome (RLS) were presented this week at the 14th International Congress of Parkinson's Disease and Movement Disorders in Buenos Aires, Argentina. Additional data from an open-label extension study showed that the efficacy of rotigotine remained stable over five years of follow up with over a third of patients remaining symptom free during that time and 96% categorized as "very much improved" or "much improved".[1-2]

"Pain has been reported by up to 60% of RLS patients.[3] These new data showed that by improving the core symptoms of RLS, rotigotine provided relief from pain and significantly improved patient wellbeing and daily activities impaired due to RLS-related pain. Therefore these data may be relevant for RLS patients with painful symptoms that are not currently being treated effectively" said Professor Ralf Kohnen, University of Erlangen-Nurembourg, Germany.

In the 6-month, double-blind study, 458 patients with moderate to severe RLS were randomised to receive either placebo or rotigotine (1,2,3 mg/24hrs) by transdermal administration.[4] Patient impairment of daily activities due to pain was assessed using Item 8 of the Quality of Life Questionnaire for RLS patients (QoL-RLS; additional exploratory endpoint). At baseline, 456 patients (99.6%) were assessed and 433 patients (94.5%) were assessed at the end of the maintenance period.[1]

At each visit, patients were asked to what degree pain in their arms or legs impaired their wellbeing or normal daytime activities on a scale of 0-5 points ("not at all" to "extremely"). The mean value for pain decreased from 2.41 to 1.85 in the placebo group, and from 2.61 to 1.39 in the rotigotine group (p=0.0003). The average change was 0 points in the placebo group, and -1 point in the rotigotine group.

Additionally, at baseline, 55.6% of the placebo group reported moderate to extreme pain, compared with 61.9% of patients in the rotigotine group. At the end of maintenance, these figures had changed to 38.2% and 22.9%, respectively.

Abstract: Rotigotine reduced impairment of daily activities due to pain in patients with idiopathic Restless Legs Syndrome[1]
Stiasny-Kolster K, Trenkwalder C, Garcia-Borreguero D, Bauer L, Grieger F, Schollmayer E, Kohnen R, on behalf of the SP790 study group
Poster Session IV, June 17th 2010, 0900-1600

Other rotigotine in RLS presentations at the Congress:

5-year results from an open-label follow-up study

Final results of the longest ever open label prospective follow-up of a placebo-controlled phase II trial in RLS have shown the safety and efficacy of rotigotine seen at previous interim analyses.[2]

This study looked at improvement in symptoms based on the International Restless Legs Syndrome Study Group Rating Scale (IRLS)*. The total IRLS score ranges from 0 (no symptoms) to 40 (very severe symptoms). A score of >20 indicates severe RLS. Of the 295 patients with moderate to severe RLS who entered the study, 126 (43%) completed the 5-year follow up. At the end of the study, 59% of patients were classified as remitters (IRLS score < 10), and 39% as symptom-free (IRLS score =0).

Additionally, the Clinical Global Impression (CGI) Improvement scale was used to assess how much the patient's illness had improved or worsened relative to baseline. The change in the condition from baseline to the end of the study was categorized as "very much improved" or "much improved" in 96% of patients. At the end of the study, 85% of patients were in a less severe illness category (normal, borderline ill or mildly ill) compared with 3% at baseline.

The mean dose of rotigotine was 2.43 mg/24 hours after initial titration and 3.09 mg/24 hours at the end of the study. Most adverse events (AEs) were mild to moderate in intensity. The most common AEs were application site reactions (58%), nasopharyngitis (19%), back pain (14%), nausea (12%) and fatigue (11%)+. Thirty per cent of patients discontinued the study due to an AE.

Abstract: Long-term safety and efficacy of rotigotine in patients with idiopathic RLS: 5-year results from a prospective multinational open-label follow-up study[2]
Högl B, Trenkwalder C, Garcia-Borreguero D, Kohnen R, Poewe W, Stiasny-Kolster K, Bauer L, Fichtner A, Schollmayer E, Oertel W, on behalf of the SP710 study group
Poster Session IV, June 17th 2010, 0900-1600

12-month results from an open-label extension study

The long-term safety and efficacy of rotigotine have also been shown in an additional 12-month open label extension study of two earlier placebo-controlled trials of rotigotine in idiopathic RLS.[5]

Of 341 patients who entered the study, 91 (27%) discontinued, 58 (17%) due to adverse events and 17 (5%) due to lack of efficacy. The most common AEs were application site reaction (33%), nausea (7%), fatigue (7%), nasopharyngitis (6%) and headache (6%)+. Mean daily dose at the start of 12-month maintenance was 2.08 mg/24hrs; after initial dose titration, 70% of patients required no further dose adjustment; 5% decreased and 25% increased their dose.

At the end of maintenance, mean IRLS score was 10.6, and 65% of patients were classified as IRLS responders (IRLS score reduced by > 50%), 55% were IRLS remitters (IRLS score of <10 points), and 30% had no RLS symptoms (IRLS score of 0).

Abstract: Safety and efficacy of long-term treatment with transdermal rotigotine in patients with idiopathic restless legs syndrome: a 12 month open-label extension study[5]
Benes H, Oertal WH, Garcia-Borreguero D, Fichtner A, Schollmayer E, Trenkwalder C, on behalf of the SP791 study group
Poster Session IV, June 17th 2010, 0900-1600

+ Please consult the Neupro® Summary of Product Characteristics for a full listing of adverse events

* The International Restless Legs Syndrome Study Group Rating Scale (IRLS)[6] is a ten-item scale developed and validated by The International Restless Legs Syndrome Study Group and considered to be the best scale for evaluating the severity and frequency of RLS symptoms and the degree to which they affect sleep and daily life. It is administered by clinicians and includes questions related to the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence and impact of RLS on activities of daily living and mood.