The investigational agent safinamide reduced the severity of dyskinesia among patients with mid- to late-stage Parkinson’s disease, according to results from a 2-year randomized trial.
"Pharmacologically, this makes sense, because safinamide, in addition to enhancing dopaminergic transmission, inhibits the stimulated release of glutamate," lead study consultant Dr. Ravi Anand said in an interview prior to the annual meeting of the American Academy of Neurology, where the research was presented. "Levodopa treatment is believed to cause glutamate release, but safinamide has been shown in animal experiments to inhibit that glutamate release. In addition, studies done in monkeys show that levodopa-induced dyskinesia can be blocked by safinamide."
Dr. Ravi Anand
Improvements in activities of daily living, quality of life, and depressive symptoms were also seen in patients who took safinamide at a dose of 100 mg/day, said Dr. Anand, a paid consultant for Bresso, Italy-based Newron Pharmaceuticals, which developed the drug before manufacturing and marketing rights were obtained by Merck Serono in 2006.
He and his associates randomized 669 patients in Europe and India with mid-to late-stage Parkinson’s disease in a phase III trial. During the 24 months of treatment, outcomes worsened among placebo-treated patients and improved in both safinamide groups, but the differences between the groups did not reach statistical significance.
A post hoc analysis of the 214 patients who had dyskinesia at baseline found that Dyskinesia Rating Scale scores among the group taking 100 mg/day of safinamide were significantly reduced by 24%, compared with placebo (P less than .05). The amount of "on" time with or without minor dyskinesia significantly increased in patients taking either 50 mg/day or 100 mg/day of safinamide (an increase of 0.67 and 0.83 hours), compared with those in the placebo group.
Significant improvements in "off" time, Clinical Global Impressions, Severity of Illness (CGI-S), GRID-Hamilton Depression Rating Scale (GRID-HAMD), and Parkinson Disease Questionnaire (PDQ-39) scores were also seen in the safinamide 100-mg/day group compared with placebo (P less than .05). Side effects were comparable among the three treatment groups. Late phase III trials of the drug are now underway.
"Dyskinesia is a terrible symptom," Dr. Anand said. "To be able to reduce that by even 5% or 10% provides great relief to the patient. The relief to the family members is also incredible."
Should it become an approved medication, the cost of safinamide is expected to be in the range of current medications such as Comtan (entacapone), Azilect (rasagiline), or Neupro (rotigotine) at $7-$10 per day, "nothing more than that, probably," Dr. Anand said.
A key limitation of the study, he said, is that only 214 of the patients had dyskinesia at baseline.
Newron and Merck Serono funded the study. Dr. Anand disclosed that he is also a paid consultant for Bioline, Roche, Pfizer, Abbott Laboratories, Takeda, and Johnson & Johnson.