Parkinson’s Drug Safinamide Submitted for Regulatory Review
Treatment has both dopaminergic and non-dopaminergic activities
A new drug application (NDA) for safinamide (Newron Pharmaceuticals/Zambon), an alpha-aminoamide, has been submitted to the FDA.
The submission covers indications for safinamide as add-on therapy to a stable dose of a single dopamine agonist in patients with early Parkinson’s disease (PD) and as add-on therapy to levodopa alone or in combination with other PD treatments in patients with mid- to late-stage PD.
Safinamide is believed to have both dopaminergic and non-dopaminergic activities, including selective and reversible inhibition of monoamine oxidase B (MAO-B), activity-dependent sodium channel antagonism, and inhibition of glutamate release in vitro.
Results from two phase III trials — MOTION and SETTLE — supported earlier findings that safinamide can improve motor function in patients with early PD receiving a single dopamine agonist at a stable dose (MOTION) and can improve motor fluctuations in patients with mid- to late-stage PD receiving levodopa and other PD drugs at a stable dose (SETTLE).
The MOTION study was a 24-week, randomized, double-blind, placebo-controlled, international phase III trial. The study enrolled patients with early idiopathic PD (disease duration of fewer than 5 years) treated with a stable dose of a single dopamine agonist for at least 4 weeks. A total of 679 patients were randomly assigned to receive once-daily safinamide (50 or 100 mg) or matching placebo as adjunctive treatment to a single dopamine agonist at a fixed dose. The trial’s primary efficacy variable was the change in motor symptoms, as assessed by the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) part III score from baseline to week 24.
The SETTLE study was also a 24-week, randomized, double-blind, placebo-controlled, international phase III trial. The study enrolled 549 patients with mid- to late-stage idiopathic PD (disease duration of more than 3 years) treated with optimized, stable doses of levodopa and standard of care (a dopamine agonist, a catechol-O-methyl transferase [COMT] inhibitor, an anticholinergic agent, and/or amantadine) for at least 4 weeks. Patients who experienced a minimum of 1.5 hours of “off” time during the day were randomly assigned to treatment with once-daily safinamide 50 mg, safinamide 100 mg, or placebo and standard of care, including levodopa, as adjunctive treatment. The trial’s primary endpoint was the change in daily “on” time, as assessed by patient-completed daily diary cards.
PD is a degenerative disorder of the central nervous system that often impairs the patient’s motor skills and speech. It is characterized by muscle rigidity, tremor, bradykinesia, and, in extreme cases, akinesia. The primary symptoms of PD result from decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high-level cognitive dysfunction and subtle language problems. PD is both chronic and progressive.
It has been estimated that more than 3 million people in industrialized countries have PD.