SILVER SPRING, MD. – A Food and Drug Administration advisory panel on Oct. 17 unanimously agreed that there was not enough evidence to support approval of rasagiline for slowing the clinical progression of Parkinson’s disease.
The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted 17-0 that the manufacturer of rasagiline, an MAO-B inhibitor, had not provided substantial evidence that the drug was effective in delaying clinical progression of the disease in patients. Rasagiline was approved in 2006 in the United States for the symptomatic treatment of Parkinson’s disease, as initial monotherapy and as adjunct therapy to levodopa; it is marketed as Azilect by Teva Pharmaceuticals Ltd.
The company conducted a study to evaluate the drug’s effects on clinical progression in about 1,100 patients with early, mild Parkinson’s, who were not on other medications for the disease. The patients (mean age 62 years) were enrolled a mean of 138 days after diagnosis and were treated with 1 mg or 2 mg of rasagiline a day or placebo for 36 weeks, at which point those on placebo were switched to 1 mg or 2 mg doses. Progression of disease was measured with the Unified Parkinson Disease Rating Scale (UPDRS).
At 72 weeks, the increase in mean UPDRS scores from baseline was smaller among patients who had been treated with the 1-mg dose from the start of the study than it was in those who had started the 1-mg dose at 36 weeks, indicating less disease progression in the former. The difference was statistically significant.
However, there was no difference in the UPDRS scores from baseline to the end of the study among those who had started the 2-mg dose at the start of the study and those who started the 2-mg dose at 36 weeks.
The FDA reviewer said that the failure of the 2-mg dose to show an effect was "troubling," and added that the results for either dose were not robust.
The panel agreed, cited other issues with the data, and voted unanimously that the study did not provide compelling evidence that the 1-mg once-daily dose was effective. While they agreed that there was an unmet need for a treatment that slowed progression and that the data were promising, they said the evidence did not meet the high bar that should be set for proving such an effect, considering the enormous public health implications of a neuroprotection claim for a Parkinson’s disease treatment.
Currently, no treatment for Parkinson’s – or any other neurologic disorder – is approved for slowing the clinical progression of the disease.
The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.