Coordinating Panel on Rare Neurological Diseases Pain

Novel Treatment for Trigeminal Neuralgia

Classical trigeminal neuralgia is a rare painful chronic disorder. Carbamazepine and oxcarbazepine are first line treatments and act by blocking sodium channels. However, their numerous side effects may prevent efficient titration.

Classical trigeminal neuralgia is a rare painful chronic disorder. Carbamazepine and oxcarbazepine are first line treatments and act by blocking sodium channels. However, their numerous side effects may prevent efficient titration.

Recently, the safety and efficacy of a novel sodium channel blocker was tested in a multi-centre phase 2a, randomised withdrawal clinical trial of 67 patients with classical trigeminal neuralgia. BIIB074 is a Nav1.7-selective, sodium channel blocker, which very likely inhibits high-frequency discharges of trigeminal ganglion neurons [1]. The importance of this new drug lies in its selectivity for the Nav1.7 channels, because there are none in the brain and consequently no central excitability depression can be caused, thus preventing the most common side effects induced by antiepileptic drugs.

The study was negative on the primary endpoint (i.e. the difference between groups in the number of patients classified as treatment failure), but several secondary endpoints were reached (e.g. there was a significant decrease in the number and severity of paroxysms in the group treated with the active drug). Therapeutic doses did not require titration and there were serious adverse events. The most common adverse events were headache and dizziness.

However, as this study used a withdrawal enrichment design, with a transition from open label to double blind phase, 70% of patients and physicians predicted their treatment during the double blind phase. In addition, 43% of the patients dropped out during the double blind phase of the study.

Nevertheless results are considered as promising particularly given the excellent tolerability of the drug and a phase-3 trial is planned.

1. Zakrzewska JM, Palmer J, Morisset V, Giblin GM, Obermann M, Ettlin DA, et al. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial. Lancet Neurol. Elsevier Ltd; 2017; 16: 291–300.