Parkinson’s disease (PD) is an age-related, progressive, neurodegenerative disease affects as many as 1 million people in the U.S. alone and up to 4 million worldwide. It is caused by the death of cells that produce dopamine, a neurotransmitter necessary for normal motor function. Parkinson's patients suffer from tremors, rigidity, slow or uncontrolled muscle movement, speech disorders, and gait and postural disturbances. Administration of drugs designed to enhance or increase endogenous dopamine levels represents the most widely used and firmly established method of treating Parkinson's disease. Various dopamine-increasing strategies have been identified, although the most widely used continues to be administration of the dopamine precursor levodopa. Long-term use of levodopa can be associated with motor complications, however. New guidelines suggest the use of dopamine agonists as opposed to levodopa as a first-line treatment in Parkinson’s disease. Dopamine agonists have been shown to delay the onset of motor complications in early PD patients.

Rotigotine hydrochloride is a dopamine D2 agonist discovered by Aderis and developed by Schwarz Pharma. It has been formulated as a transdermal patch designed to circumvent one of the major problems encountered with oral medications, namely inconsistent pharmacokinetics, leading to fluctuating efficacy and side effects. The rotigotine transdermal patch delivers a constant drug level for 24 hours, at which time it is replaced with a new patch. In October, Schwarz Pharma submitted applications in the U.S. and E.U. seeking marketing approval for rotigotine (Neupro^TM) for the treatment of patients in early stages of Parkinson's disease. Further testing is underway in patients with more advanced-stage disease. More than 1,500 patients with Parkinson's disease have been treated to date with rotigotine in 15 clinical trials.

In one such study, results of which were also communicated in October, rotigotine showed a statistically significant and clinically relevant reduction in “off” time in patients with advanced PD. The reduction in off time following adjunctive therapy with rotigotine was not associated with an increase in undesirable dyskinesias. In the U.S. phase III trial, 351 patients with advanced-stage idiopathic PD received active drug or placebo in addition to stable levodopa treatment. The primary parameters were change from baseline in the absolute off time and response rate (response being defined as at least a 30% decrease in absolute off time from baseline). The most common adverse events associated with the use of rotigotine transdermal system were application site reactions, somnolence, nausea and dizziness. A total of 99% of patients who completed the trial opted to continue treatment with rotigotine during an open-label extension trial.

Earlier in the year, the Parkinson Study Group reported the results of a randomized, multicenter, double-blind, placebo-controlled study that included 242 patients older than 30 years with idiopathic PD and a Hoehm and Yahr stage equal to or lower than 3. Patients were treated with placebo or rotigotine administered transdermally for up to 11 weeks. Compared to placebo, patients treated with rotigotine showed significant improvements in UPDRS scores after only four weeks of treatment which were maintained throughout the study. Adverse events most frequently associated with rotigotine included nausea, application site reactions, dizziness, somnolence, insomnia, vomiting and fatigue. Four out of nine serious adverse events were considered to be drug-related. The authors concluded that transdermal rotigotine monotherapy was well tolerated and effective in improving the signs of early PD.

Rotigotine is also being actively studied for the treatment of restless legs syndrome (RLS), another disorder that often responds favorably to dopaminergic therapy. In a multinational phase IIb study reported earlier this year, rotigotine therapy was associated with statistically significant and clinically relevant reductions in RLS symptoms. A meaningful clinical effect was observed within the first seven days of treatment, and the patch was well tolerated. The multicenter, double-blind, placebo controlled trial had a treatment duration of six weeks. In total, 310 patients with idiopathic moderate to very severe RLS completed the trial. Schwarz is now preparing the phase III program, which is scheduled to start in spring 2005.