A large phase III clinical trial conducted across 21 medical centers in China has found that generic brivaracetam, an anti-seizure medication taken as an add-on therapy, substantially reduced seizure frequency in adults with focal-onset seizures. The randomized, double-blind, placebo-controlled study, published in Acta Epileptologica, enrolled 179 patients and compared a 200 mg daily dose of the generic tablet against placebo over a 12-week treatment period.
Focal-onset seizures are among the most common seizure types in adults. Epilepsy itself is a chronic brain disorder characterized by recurrent, unprovoked seizures, and it affects an estimated 50 million people worldwide, making it the second most common disorder of the central nervous system. Despite decades of drug development, existing anti-seizure medications leave roughly one-third of patients inadequately treated, either because their seizures remain refractory or because side effects make long-term therapy difficult to tolerate. This persistent treatment gap is what motivated the search for newer agents with better efficacy and tolerability profiles.
Brivaracetam works through a mechanism shared with the older drug levetiracetam: both bind to synaptic vesicle protein 2A, or SV2A, a protein involved in the cycling of synaptic vesicles that release neurotransmitters inside neurons. By interacting with SV2A, brivaracetam modulates neurotransmitter release and thereby exerts an anti-seizure effect. Preclinical experiments had shown that brivaracetam displayed significant anti-seizure activity in animal models and appeared more effective and safer than other SV2A ligands, including levetiracetam. Earlier clinical trials and real-world observations, however, were conducted mostly in high-income countries, and rigorous evidence in large samples of Chinese patients had been lacking. The new trial was designed to fill that gap while also evaluating a generic formulation, a point with practical consequences for drug access.
The study was a therapeutic confirmatory trial registered as CTR20202124 and conducted in accordance with Good Clinical Practice requirements and the Declaration of Helsinki. Eligible patients were between 16 and 80 years old with uncontrolled focal-onset seizures, with or without secondary generalization, despite stable treatment with one or two permitted concomitant anti-seizure medications. Participants had to have experienced at least eight focal seizures in the eight weeks before treatment, with at least two seizures every four weeks and no seizure-free interval longer than 21 days. The trial began with an eight-week baseline period, combining a four-week retrospective seizure diary with a four-week prospective recording phase, after which patients were randomized one to one to receive either brivaracetam 200 mg per day, taken as 100 mg in the morning and evening, or a matching placebo.
Over the 12-week double-blind treatment period, the primary efficacy endpoint was the percent reduction in focal seizure frequency per 28 days from baseline. Secondary endpoints included the responder rate, defined as the proportion of patients achieving at least a 50 percent reduction in seizure frequency; the distribution of patients across different levels of seizure reduction; the time from the start of treatment to the first, fifth, and tenth seizures; and the percentage of patients who achieved seizure freedom. Safety was monitored through adverse event reporting, clinical symptoms, vital signs, physical examinations, laboratory tests, electrocardiograms, and the Columbia-Suicide Severity Rating Scale administered at each follow-up visit through week 15, followed by a four-week down-titration phase.
Of the 241 patients screened, 179 were randomized, and 178 entered the final analysis after one placebo patient who never received the study drug was excluded. The full analysis set comprised 90 patients on brivaracetam and 88 on placebo. Overall, 155 patients, or 87 percent, completed the trial, with discontinuation rates of 12.22 percent in the brivaracetam group and 11.24 percent in the placebo group. Baseline characteristics, including demographics, epilepsy history, and comorbidities, were well balanced between the groups. Median seizure frequency per 28 days fell from 9.16 at baseline to 4.07 during treatment in the brivaracetam group, while the placebo group declined from 8.50 to 6.96, producing the headline 40.67 percent relative reduction.
The responder results reinforced the primary finding. Nearly 49 percent of brivaracetam patients achieved at least a 50 percent reduction in seizure frequency, compared with 23.86 percent on placebo, an odds ratio of 3.12 with a 95 percent confidence interval of 1.63 to 5.99 and a p-value of 0.0006. Seizure freedom during the complete treatment period was achieved by 10 patients, or 11.11 percent, in the brivaracetam group versus 2 patients, or 2.27 percent, on placebo, a statistically significant difference. The median time to the first, fifth, and tenth focal seizures was also significantly longer in the brivaracetam group, indicating that the drug delayed the recurrence of seizures across multiple thresholds of cumulative seizure burden.
Safety data painted a more nuanced picture. Sixty-three brivaracetam patients and 49 placebo patients reported adverse events, a difference of 70.00 percent versus 55.68 percent that did not reach statistical significance. However, discontinuations due to adverse events were higher with brivaracetam, at 6.67 percent versus none in the placebo group, and adverse events of special concern, defined according to Chinese regulatory guidance for epilepsy drug trials, occurred in 32.22 percent of brivaracetam patients versus 9.09 percent on placebo. Side effects followed a similar pattern, reported by 52.22 percent of brivaracetam patients versus 28.41 percent on placebo. The most common adverse events were dizziness, seen in 23.33 percent of brivaracetam patients versus 7.95 percent on placebo, somnolence at 13.33 percent versus 3.41 percent, and nausea, which affected seven brivaracetam patients and none on placebo. No significant differences emerged in laboratory parameters, vital signs, body weight, electrocardiograms, physical examinations, or psychiatric status.
The authors placed their findings in international context. A previous multi-center trial in Asian patients treated with brivaracetam 200 mg per day reported a 33.4 percent reduction in seizure frequency and a 49.3 percent responder rate, while a global trial spanning North America, Western and Eastern Europe, Latin America, and Asia reported a 23.2 percent reduction over placebo and an odds ratio of 2.19 for the 50 percent responder rate. A pooled analysis of three clinical studies found a 24.0 percent reduction over placebo and a responder rate of 37.8 percent versus 20.3 percent for placebo. The 40.67 percent reduction observed in the Chinese trial therefore appears higher than some earlier international results, a discrepancy the authors attribute tentatively to differences in recruitment criteria, concomitant medications, or genetic factors among participants, while cautioning that this possibility limits direct comparison.
The trial also carried explicit limitations that shape how the results should be read. The authors note possible recall bias in patient-recorded seizure diaries, a relatively short treatment and follow-up period that precluded assessment of long-term efficacy and safety, the absence of detailed mood, cognitive, and quality-of-life evaluations, and the testing of only a single fixed dose without titration or dose-ranging. Notably, levetiracetam users were excluded, even though levetiracetam is one of the most widely prescribed anti-seizure medications in China and in low- and middle-income countries, and the study used the older 1981 ILAE seizure classification rather than current frameworks. Despite these caveats, the authors conclude that generic brivaracetam demonstrated better efficacy and comparable safety in treating focal-onset seizures in Chinese patients, and they argue that the development of generic formulations may reduce health care costs and improve drug accessibility in low- and middle-income countries, where over 80 percent of people with epilepsy live and where proprietary medications remain prohibitively expensive for most. Larger trials with longer follow-up, they add, will be needed to evaluate effects on mood, cognition, and quality of life.
Subject of Research: A phase III randomized trial evaluating generic brivaracetam as adjunctive therapy for focal-onset seizures in Chinese adults
Article Title: Efficacy and safety of Brivaracetam as an adjunctive therapy in patients with focal-onset seizures: a phase III, multi-center, randomized, double-blind, placebo-controlled trial
Article References: Yu, P., Zhao, T., Lin, W., Han, X., Li, F., & Hong, Z. (2026). Efficacy and safety of Brivaracetam as an adjunctive therapy in patients with focal-onset seizures: a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Acta Epileptologica, 8(1), Article 21. https://doi.org/10.1186/s42494-026-00253-7
Image Credits: AI Generated
DOI: 10.1186/s42494-026-00253-7
Keywords: brivaracetam, epilepsy, focal-onset seizures, phase III trial, anti-seizure medications, SV2A, randomized controlled trial, generic drugs, placebo-controlled, China, seizure frequency, drug safety
News Source: Ophelia Keating. (October 30, 2026). Generic Brivaracetam Cuts Seizure Frequency in Chinese Phase III Trial. Scienmag.
