New research data on pramipexole report effectiveness and long-term relief from the symptoms of Restless Legs Syndrome

Denver, Colorado, June 20, 2005 - New data reported today at the 19th Annual Meeting of the Associated Professional Sleep Societies (APSS) in Denver, CO demonstrate that Boehringer Ingelheim's dopamine agonist, pramipexole, substantially reduced the severity of Restless Legs Syndrome (RLS) symptoms in pramipexole-treated patients suffering from RLS¹. The results were presented from three analyses of two clinical studies investigating the effects of pramipexole in RLS patients.

Pramipexole is currently approved for the treatment of Parkinson's disease and is being evaluated in clinical trials as a potential treatment for reducing the symptoms of RLS. RLS is a common, but poorly recognized and under-treated neurological disease that predominantly affects adults. Based upon positive clinical results, Boehringer Ingelheim anticipates submitting a New Drug Application to the U.S. Food and Drug Administration later this year.

Long-term effect of pramipexole

In one long-term, prospective, uncontrolled, open label study presented during the symposium, 97 RLS patients were followed for 30 weeks to assess the sustained effect of pramipexole on RLS symptoms. The symptoms were assessed using two different instruments: the Restless-Legs-Syndrome Rating Scale (RLSRS) and the Clinical Global Impression Improvement (CGI-Improvement) scale -- the first by clinical interview and the second by the patients' physician. In these patients, there was significant improvement in RLS symptoms after six months of treatment with pramipexole compared to baseline:

95 percent of patients were assessed by physicians as having a 'much improved' or 'very much improved' condition versus baseline on the CGI-Improvement scale.¹
The mean overall RLSRS score was reduced by 16.9 points compared to baseline at the end of therapy (p<0.05).¹

Professor Markku Partinen, M.D., Ph.D., Director and Chief Neurologist at the Skogby Sleep Clinic and Associate Professor in Neurology at the University of Helsinki, Finland, commented, "We have seen in previous studies that pramipexole can provide marked and rapid relief from RLS symptoms - which is important for patients who want their treatment to work quickly - but what we did not know until now was whether pramipexole keeps working over a long period of time. These new data suggest that pramipexole has a long-lasting effect in RLS."

Short-term effects of pramipexole

Dr. Svenja Happe, Department of Clinical Neurophysiology, University of Göttingen, Germany, analyzed responses to item 9 of the RLS rating scale, which asks the patient about the impact of RLS on the ability to carry out daily affairs, as well as the quality of life scale, SF-36. Of a total of 345 patients in a six-week, double-blind, placebo-controlled study, 58 patients reported a severe impact of RLS on their ability to carry out daily affairs at baseline. Analyses of these 58 patients after 6 weeks of treatment showed that:

Over half of the patients receiving pramipexole (58.4 percent) reported that their RLS symptoms had either 'no impact' or 'mild impact' on their daily affairs (item 9 in the RLSRS scale) compared to 27.2 percent of patients who received placebo (p=0.0305).^2,3
Social functioning improved more in the pramipexole group as compared to placebo with a mean change from baseline on the SF-36 of 6.0 versus 0.8 points (p=0.016).^2,3

From this same six-week, double-blind, placebo-controlled study, Dr. Svenja Happe analyzed responses to item 7 of the RLS rating scale, which asks about the frequency of RLS symptoms in the week before assessment. Of a total of 345 patients in this study, 187 patients suffered very often from RLS symptoms at baseline. Analyses of these 187 patients after 6 weeks of treatment showed that:

Significantly more patients treated with pramipexole were symptom-free during the last of treatment as compared to the placebo group (29/123; 23.6% vs. 4/64; 6.3%, p=0.0019).³

Since the first exploratory placebo-controlled cross-over trial involving pramipexole in 1999⁴, several open-label, retrospective studies on the efficacy and safety of pramipexole in RLS patients have been reported^5-7. These studies suggested that pramipexole may be efficacious and reasonably tolerated for RLS.⁸ The effect of pramipexole in RLS is being investigated in a comprehensive ongoing clinical trials program in approximately 1,000 patients to further assess the therapeutic potential in this condition. Currently, pramipexole is not approved for the treatment of Restless Legs Syndrome (RLS). Boehringer Ingelheim, the discoverer of the molecule, plans to submit for international regulatory approval of pramipexole for RLS in the second half of 2005.

About pramipexole

Pramipexole, a compound from Boehringer Ingelheim research, was jointly developed by Boehringer Ingelheim and Pharmacia Corp. (today Pfizer). Currently, pramipexole is approved in the U.S. for the treatment of the signs and symptoms of idiopathic Parkinson's disease, as monotherapy or in combination with levodopa. The most commonly reported adverse events in early and late Parkinson's disease in clinical trials were dizziness, dyskinesia, extrapyramidal syndrome, headache, insomnia, somnolence, and nausea. Hallucinations and postural (orthostatic) hypotension may occur. Patients have reported falling asleep without perceived warning signs during activities of daily living, including operation of a motor vehicle, which sometimes resulted in accidents.

Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 144 affiliates in 45 countries and nearly 36,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2004, Boehringer Ingelheim posted net sales of US $10.2 billion (8.2 billion euro) while spending nearly one fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

For more information, please visit http://us.boehringer-ingelheim.com.

Notes to Editors

RLS - Restless Legs Syndrome
RLS is a neurological disorder characterized by an uncontrollable urge to move the legs, usually accompanied by unpleasant and sometimes painful sensations in the legs. RLS affects up to ten percent of the adult population9 and around one-third of sufferers experience symptoms more than twice weekly causing moderate to severe distress¹⁰. The motor-restlessness worsens during the evening and night causing difficulty initiating and maintaining sleep. The sleep disruption can lead to excessive daytime sleepiness and compromise work performance. RLS also has considerable impact on social activities that require immobility^11,12.

RLSRS - RLS Rating Scale

CGI - Clinical Global Impression Improvement Scale
The CGI Improvement scale is a clinical-rated instrument that consists of four subscales. The CGI Improvement scale is traditionally used as an endpoint in clinical trials for responder analyses while the other subscales are less used. The global assessment of overall severity of illness, of the overall therapeutic effect and of interference of side effects with functioning, provides additional information of the overall effectiveness of a drug treatment.

SF-36 - Short-form 36 items quality of life assessment

Contact:

Katherine O'Connor
Manager, Communications & Public Relations
Boehringer Ingelheim Pharmaceuticals, Inc.
Phone: +1 (203) 791-6250
Email: koconno4@rdg.boehringer-ingelheim.com

Partinen et al. Beneficial effect of PPX in RLS patients after 6 months treatment-Results from a prospective open label study; presented 22 June 2005, 1:30 - 2:15pm APSS 19th Annual Meeting, Denver, Colorado; Abstract, ID # 132978:
Happe et al. Increase of symptom free days for RLS patients by treatment with Pramipexole; presented 22 June 2005, 1:30 - 2:15pm APSS 19th Annual Meeting, Denver, Colorado; Abstract, ID # 133048:
Happe et al. Pramipexole reduces the impact of RLS symptoms; presented 22 June 2005, 1:30 - 2:15pm APSS 19th Annual Meeting, Denver, Colorado; Abstract, ID # 133045:
Montplaisir J et al B Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology 1999; 52 (5) , 938-943
Silber MH et al Pramipexole in the management of restless legs syndrome Sleep 2003; 26(7): 819-821
Winkelman JW; Johnston L Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med 2004; 5 (1), 9-14
Ferini-Strambi L Restless legs syndrome augmentation and pramipexole treatment Sleep Medicine 2002; 3(1): S23-S25.
Oertel W, Stiasny-Kolster K. Early and persistent effect of pramipexole in RLS patients already with the starting dose. Movement Disorders 2005, 20 (Suppl 10): S58 9. Phillips B et al Epidemiology of restless legs symptoms in adults Arch Intern Med 2000; 160(14): 2137-2141
Hening W et al Impact, diagnosis and treatment of restless legs syndrome in a primary care population: the REST (RLS epidemiology, symptoms and treatment) primary care study Sleep Med 2004; 5(3): 237-246
Allen RP Earley CJ Restless legs syndrome: a review of clinical and pathophysiologic features J Clin Neurophysiol 2001; 18(2): 128-147
Earley CJ Clinical practice. Restless legs syndrome New Engl J Med 2003: 348(21) ; 2103-2109