Newron Pharmaceuticals, based in Milan, Italy, has resubmitted a new drug application for safinamide (Xadago) to the FDA. Safinamide is a selective, reversible monoamine oxidase B (MAO-B) inhibitor capable of blocking voltage-dependent sodium channels, which in turn modulates the abnormal release of glutamate, in patients with Parkinson’s disease (PD).
The FDA had communicated to Newron in a meeting in July that clinical studies to evaluate the potential abuse liability or dependence/withdrawal effects of safinamide were no longer required. The meeting had been scheduled after the FDA issued a complete response letter in March. As a class 2 resubmission, the FDA is expected to complete its review of the new application within six months of acceptance.
Results from 24-month, double-blind, controlled studies showed that safinamide had statistically significant effects on motor fluctuations (on/off time) without increasing the risk of developing troublesome dyskinesia. These effects may be related to actions on both dopaminergic and glutamatergic pathways. Safinamide is administered once daily and has no dietary restrictions because of its high MAO-B selectivity. The rights to develop and commercialize safinamide in the U.S. have been granted to US WorldMeds.
PD is the second most common chronic progressive neurodegenerative disorder in the elderly after Alzheimer’s disease, affecting 1% to 2% of individuals 65 years of age or older worldwide. The diagnosis of PD is mainly based on observational criteria of muscular rigidity, resting tremor, or postural instability in combination with bradykinesia. As the disease progresses, symptoms become more severe.
L-dopa (L-3,4-dihydroxyphenylalanine) remains the most effective treatment for patients with PD. Long-term treatment, however, can lead to debilitating motor fluctuations, i.e., phases of normal functioning (on-time) and decreased functioning (off-time). In addition, many patients experience involuntary movements known as L-dopa–induced dyskinesia (LID). As the disease progresses, clinicians focus on treating symptoms while managing LID and the “off-time” effects of L-dopa. Most of the current PD therapies act by increasing dopaminergic transmission, which ameliorates motor symptoms.
Source: Newron Pharmaceuticals; September 22, 2016.