Adjunctive treatment with natalizumab did not change seizure frequency in a small sample of patients with severely drug-resistant focal epilepsy, but no unexpected safety findings were reported, according to a phase 2 study results published in Neurology.
For patients who failed to achieve sustained seizure freedom following adequate trials of 2 anti-seizure drugs, surgery, neurostimulation, specialized diets and/or other therapies may be employed. The current study aimed at assessing the safety and efficacy of natalizumab as adjunctive therapy in adults with drug-resistant epilepsy.
The randomized, placebo-controlled, double-blind, phase 2 (OPUS; ClinicalTrials.gov Identifier: NCT03283371) included patients from 31 sites across the United States with drug-resistant focal epilepsy with 6 or more seizures during the baseline period. The study consisted of a 6-week prospective baseline period followed by a double-blind, placebo-controlled period where participants were randomized 1:1 to receive intravenous natalizumab 300 mg or placebo every 4 weeks for 24 weeks.
Change from baseline in log-transformed seizure frequency was the primary efficacy endpoint, with a pre-defined threshold for therapeutic success of 31% relative reduction in seizure frequency over the placebo group participants. Incidence of adverse events and serious adverse events were determined to assess treatment safety.
The study sample included 30 patients in the natalizumab and 31 patients in the placebo group who completed the placebo-controlled treatment period.
The least squares mean change from baseline in log-transformed seizure frequency from weeks 8 to 24 was -0.58 for natalizumab and -0.43 for placebo, corresponding to a relative change over placebo of -14.4% (95% CI, -46.1% to 36.1%; P =.51). The proportion of participants with a 50% or more reduction from baseline in seizure frequency in the same period was 31.3% for natalizumab and 17.6% for placebo (odds ratio, 2.09; 95% CI, 0.64-6.85; P =.22).
There were no unexpected safety findings with adverse events reported in 24 (75%) natalizumab-treated patients and in 22 (65%) participants in the placebo group. Serious adverse events were reported in 1 participant (3%) in each group. There was only 1 incidence (urticaria) of an adverse event leading to treatment discontinuation in the natalizumab group.
Study limitations included the small sample size, and the higher proportion of patients with focal to bilateral tonic-clonic seizure observed during the baseline period in the placebo group with potential downsizing the effect of natalizumab.
“Despite not meeting the efficacy threshold, there were no unexpected safety findings, and pharmacodynamic evidence indicating a consistent mechanism of action suggests that there is good reason to continue exploring agents that target inflammatory processes specific to the CNS to manage drug-resistant epilepsy,” concluded the researchers.
Disclosure: This research was supported by Biogen Inc. Please see the original reference for a full list of disclosures.
French JA, Cole AJ, Faught E, et al. Safety and efficacy of natalizumab as adjunctive therapy for people with drug-resistant epilepsy: a phase 2 study. Neurology. Published online, November 2, 2021. doi: 10.1212/WNL.0000000000012766