A Phase III trial testing the long-term efficacy of safinamide as an add-on treatment to dopamine agonist therapy in patients with early stage Parkinson's disease ended unsuccessfully, Newron Pharmaceuticals and Merck Serono said.
The primary endpoint, time to intervention, did not reach statistical significance when data from two dosage groups, 50 mg to 100 mg and 150 mg to 200 mg, were pooled, the firms said.
The study was a 12-month extension of a six-month Phase III trial testing the long-term safety and efficacy of safinamide as an add-on treatment to dopamine agonist therapy.
Results announced in May from the six-month trial showed that low dosages of safinamide improved motor function in patients taking the drug as an add-on treatment to dopamine agonist therapy, Ravi Anand, Newron's chief medical officer, noted during a conference call.
Although the 18-month study did not reach its endpoint, the long-term efficacy and safety data for the low-dosage group were "encouraging," said Newron CEO Luca Benatti. He noted that the six-month data are all that is required for U.S. approval decisions.
For the 18-month trial, patients were randomized to the two dosage groups or a placebo-controlled group as an add-on treatment to dopamine agonist therapy.
Patients who entered the initial six-month Phase III trial could continue the study for an additional year, receive other treatments for Parkinson's disease, or could discontinue therapy.
Of the 270 patients enrolled in the original trial, 227 entered the 12-month extension. Of those, 187 patients completed the extension period.
Merck Serono, of Geneva, and Newron, of Bresso, Italy, said the lack of a significant effect in the 18-month data might be explained by the lack of response with the high-dose group as seen in the analysis of the first six months. A post-hoc analysis, the firms stated, showed that the addition of safinamide at a dose of 50 mg to 100 mg once daily to dopamine agonist therapy significantly reduced the number of patients who experienced an intervention, maintained improvement in motor symptoms and improved quality of life compared with dopamine agonist monotherapy.
The primary efficacy endpoint of the 18-month trial was time from baseline to intervention. Intervention was defined by the onset of increase in dose of dopamine agonist; addition of another dopamine agonist, levodopa or another Parkinson's disease therapy; or discontinuation due to lack of efficacy.
Anand said that the drug was well tolerated in patients and adverse events in the 12-month extension trial did not increase in severity from those reported in the six-month trial.
The most frequently reported adverse events were back pain, peripheral edema and dizziness, he noted.
"In my opinion, this is a very positive drug," Anand said.
A Phase III trial evaluating safinamide at the 50 mg to 100 mg once daily dose range as add-on to levodopa therapy is ongoing in patients with mid-to-late stage Parkinson's disease, Anand said.
Additional Phase III trials evaluating the low dosage of safinamide either as add-on to dopamine agonist or as add-on to levodopa therapy in patients with mid-to-late stage Parkinson's disease also are planned, he added.
Under a September 2006 agreement with Newron, Merck Serono acquired the exclusive worldwide rights to develop, manufacture and commercialize safinamide in Parkinson's disease, Alzheimer's disease and other cognitive disorders.