Oxcarbazepine, an anti-epileptic medicine, given in combination with a disease-modifying therapy (DMT) may help to stop disability progression in multiple sclerosis (MS) patients, results of Phase 2 trial suggest.

Monica Marta, PhD, with Queen Mary University of London and Barts Health NHS Trust/The Royal London Hospital presented the data at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), recently held in Stockholm, (Sept. 11–13).

The presentation was titled “ Oxcarbazepine as a neuroprotective agent in MS: a phase IIa trial (PROXIMUS) .”

Neurodegeneration in people with MS is triggered by both immune-dependent and independent mechanisms. The efficacy of therapies that aim to prevent the loss of neurons is known to be superior when given at early disease stages. However, assessing the degree of nerve loss is challenging at these initial stages.

In a previous study, researchers showed that treatment with a sodium channel blocker, called oxcarbazepine, limited neuron loss in a mouse model of MS. Oxcarbazepine, sold as Trileptal (among other brand names), is an anti-epileptic medicine used to treat seizures.

“We know sodium channels are affected in MS,” Marta said. Previous studies in mouse and human models of MS showed that “sodium channels blockers have … an effect as neuroprotective,” she added.

In the Phase 2 PROXIMUS trial (NCT02104661), researchers in the U.K. assessed the neuroprotective potential of oxcarbazepine in MS patients as an add-on therapy to their standard DMT regimen.

“The idea behind the clinical trial [PROXIMUS] is that in order to achieve some form of neuroprotection, we have to start with an anti-inflammatory effect,” Marta said.

“Can axonal degeneration be prevented by partial blockade of sodium channels using oxcarbazepine in people with MS who are relapse-free on DMT but have disability deterioration?” the researcher asked.

The team measured the levels of neurofilament light chain (NfL) in the cerebrospinal fluid (CSF) of MS patients. NfL is exclusively present in nerve cells, and its presence in the blood or CSF is a sign of neuronal degeneration.

Researchers also measured patients’ disability using the Expanded Disability Status Scale (EDSS) scores, and evaluated brain images obtained by coherence tomography and magnetic resonance imaging (MRI). They also looked at patient self-assessments, including the Multiple Sclerosis Walking Scale (MSWS) questionnaire, which measures the impact of MS on walking.

The PROXIMUS trial recruited 30 relapsing MS patients, who were without relapses but felt they were getting worse. Patients had NfL levels at the trial’s start of at least 380 pg/mL in their CSF. They were randomized to receive oxcarbazepine or a placebo twice a day, added to their standard DMTs. (All were taking a DMT for at least six months prior to baseline, or trial start, and had no relapses during that period.) NfL levels in the CSF were measured at baseline, and again after 25 and 48 weeks (the study’s end). The trial’s main goal was to measure the decrease in NfL levels in the CSF at 48 weeks relative to the placebo control group. Results showed no differences in NfL levels between the groups after adjusting the values to those at the trial’s start. “Unfortunately, our primary endpoint was not achieved,” Marta said. “There was no difference in the baseline adjusted CSF NfL levels at 48 weeks between oxcarbazepine versus placebo-treated MS patients.”

However, patients given oxcarbazepine had significantly lower EDSS scores compared to the control group, meaning a reduction in disability levels.

In agreement with these findings, oxcarbazepine-treated patients showed lesser disease progression, as evidenced by their reported performance in the MS walking scale. No effects were detected on MRI brain scans.

Results showed that “oxcarbazepine had no effect on CSF NFL levels in our cohort,” but “there was a significant clinical treatment effect as measured by EDSS and MSWS scores at 48 weeks,” Marta said.

Marta told Multiple Sclerosis News Today that the team plans to continue investigating neuroprotective agents, “and try to gain further insights about their effect in MS patients.”

PROXIMUS was funded by the National MS Society, and Novartis supplied Trileptal (oxcarbazepine) free of charge.