NEW ORLEANS – A reformulated version of the previously withdrawn Neupro rotigotine patch had favorable results in separate studies of patients with advanced idiopathic Parkinson’s disease and restless legs syndrome, according to reports given prior to the planned return of the patch to the U.S. market in July.
The dopamine agonist patch was originally approved by the Food and Drug Administration in 2007 for early-stage idiopathic Parkinson’s disease, but UCB Pharma withdrew it from the U.S. market in 2008 because rotigotine was crystallizing out of the delivery matrix. The agency approved a reformulated version in April along with revised labeling that now indicates Neupro for all stages of idiopathic Parkinson’s, plus moderate to severe primary restless legs syndrome (RLS).
The return of the patch is "terrific news for the Parkinson’s disease community. ... Because Parkinson’s disease patients typically have to take many doses of medications each day, the re-approval of the patch will hopefully help a lot of sufferers," by cutting pill burden, among other things, said Dr. Michael Okun, medical director of the National Parkinson Foundation, in a written statement.
In a 16-week, randomized trial involving 514 advanced idiopathic Parkinson’s disease (PD) patients, 8 mg/24 hours reduced off-time by 2.4 hours per day after 12 weeks of maintenance therapy, a statistically significant benefit over placebo, which reduced off-time by 1.5 hours. Lower patch doses reduced off-time as well, but not significantly better than did placebo. All patients in the trial were on levodopa; other medications were allowed. Off-time was assessed by home diaries.
The benefit of 8 mg/24 hour is in line with the new label, which recommends that dosage for advanced Parkinson’s, and 6 mg/24 hours for early-stage disease. The recommended RLS dosage is up to 3 mg/24 hours.
The label details two clinical trials for RLS. In one involving 505 patients, scores on the 40-point IRLS (International RLS) rating scale improved by 14.2 points in patients who were randomized to 3 mg/24 hours for 6 months, whereas placebo improved scores by 9 points. That difference was statistically significant, as were lower Neupro doses. UCB fleshed out the results at the annual meeting of the American Academy of Neurology, noting the magnitude of statistically significant improvements, compared with placebo, in individual components of the IRLS, such as sleep disturbances (0.4-point improvement over placebo on a 5-point scale), impact on daily activities (0.3-point improvement over placebo on a 5-point scale), and frequency of symptoms (0.9-point improvement over placebo on a 5-point scale).
The company also presented post hoc analyses of previous trials that showed that Neupro may help fatigue, apathy, anhedonia, anxiety, and depression in PD. Another post hoc analysis of a 287-patient trial suggested that it might also help with pain; PD patients with a score equal to 1 (any pain) on a 10-point Likert pain scale had a 0.54-point improvement over placebo after being maintained at 2-16 mg/24 hours for 4 weeks.
The patch’s new labeling adds advice on discontinuing the drug, as well as information about the risk of augmentation and rebound in RLS, plus additional detail on somnolence, hypotension, hallucination, impulse control disorder, and other possible side effects.
In the recent randomized trial of 514 patients with PD, "the most common adverse events included application site reactions [15% vs. 7% placebo], nausea [12% vs. 7% placebo], and dyskinesias [8% vs. 3% placebo]. The remainder of the safety profile was similar to previous studies of rotigotine in patients with advanced Parkinson’s," said Dr. Lawrence Elmer, medical director of the center for neurological disorders at the University of Toledo (Ohio), who presented the findings at the meeting.
Dr. Elmer disclosed unrestricted educational grants and payments for consulting, advisory, and speaking services from UCB Pharma and other pharmaceutical companies. Dr. Okun had no current, relevant disclosures.