Eisai (Italy)

Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.

In the treatment of pediatric epilepsy, there is a critical demand for effective and safe therapeutic options to address patients' unmet clinical needs. Eslicarbazepine acetate is a novel once-daily antiepileptic drug and a third-generation single enantiomer member of the dibenzazepine family. The objective of this study was to evaluate the efficacy and safety of eslicarbazepine acetate as add-on treatment for focal-onset seizures in pediatric patients using meta-analytical techniques. Randomized, placebo-controlled, single- or double-blinded add-on trials of eslicarbazepine acetate in patients < 18years of age with focal-onset seizures uncontrolled by concomitant stable antiepileptic drug regimens were identified through a systematic literature search. The assessed outcomes included the mean relative change and ≥ 50% reduction in the baseline seizure frequency, the incidence of treatment withdrawal, serious adverse events, and treatment-emergent adverse events. Risk ratio and weighted mean difference with 95% confidence intervals were estimated for dichotomous/continuous outcomes. Two trials were included involving 386 participants (age range 2-18years), 217 for eslicarbazepine acetate and 169 for placebo groups, respectively. At the dosage of 30mg/kg/day, eslicarbazepine acetate-treated patients had a significantly greater reduction in baseline seizure frequency (weighted mean difference - 21.67, 95% confidence interval - 40.87 to - 2.46; p = 0.027) and 58 patients (44.6%) were seizure responders compared with 27 controls (29.7%) [risk ratio 1.48, 95% confidence interval 0.99-2.20; p = 0.055]. There were no differences in treatment withdrawal (risk ratio 1.24, 95% confidence interval 0.65-2.37; p = 0.513), serious adverse events (risk ratio 1.40, 95% confidence interval 0.69-2.86; p = 0.350), and treatment-emergent adverse events (risk ratio 1.07, 95% confidence interval 0.94-1.22; p = 0.313). Adjunctive eslicarbazepine acetate could be an effective well-tolerated option in children and adolescents with focal-onset seizures uncontrolled by one or more concomitant anti-epileptic drugs.

The purpose of this study was to determine the distribution profile of a novel endotoxin antagonist, [(14)C]E5531, at 1 microg/ml in plasma samples obtained from fasted human subjects with various lipid and protein concentrations. Our findings suggest that the majority of E5531 binds with high-density lipoproteins (HDLs) independently of plasma lipid and protein levels tested. Furthermore, it appears that an increase in triglyceride-rich lipoprotein (TRL) lipid and protein levels and an increase in low-density lipoprotein (LDL) lipid levels significantly increase TRL plus LDL binding of E5531. However, only an increase in HDL protein levels significantly increases HDL binding of E5531.