Safinamide

In 2017, the FDA approved safinamide (marketed at Xadago), the first new chemical entity approved for treatment of primary Parkinson’s disease symptoms in a decade.

Safinamide

Overall, the response from the medical and patient communities has been muted, probably in part because its path to regulatory approval, first in Europe and then in the US, was long; it appears to have entered phase 3 clinical trials as early as 2007. The clinical results, while positive, were somewhat underwhelming. Thus far, the benefits appear to be similar to other MAO-B inhibitors, and it is likely to be used in a similar fashion, i.e., primarily as an adjunct to treatment with levodopa, to (modestly) increase on-time without dyskinesia.

safinamide-clinical trial

It does have some novel features, however.  Unlike rasagiline and selegiline before it, safinamide binds MAO-B reversibly, i.e., it does not form a covalent bond with the protein.  Whether this provides any clinical advantage (or disadvantage) is not clear, but it is a significant distinguishing feature, in addition to the very different chemical structure.  The more important novel aspect is that safinamide also modulates sodium and calcium channels, dopamine re-uptake (after it is released from a neuron), and glutamate signaling.  The latter is potentially significant because of the role of glutamate signaling in dyskinesias.  However, the evidence for the more complex pharmacology of safinamide having therapeutic relevance, vis a vis its action on MAO-B, is thus far indirect.  Patient experience, and potentially additional clinical trials, may eventually provide greater clarity about the strengths and weaknesses of this new drug and its role in the symptomatic treatment of Parkinson’s disease.