Brivaracetam benefits Asian adults with uncontrolled focal-onset seizures

Adjunctive brivaracetam (BRV) reduces seizure frequency and improves response in Asian adults with uncontrolled focal-onset seizures (FOS), findings from the phase III therapeutic confirmatory EP0083 study suggest.

“The primary efficacy endpoint (percent reduction in 28-day FOS frequency vs placebo over the 12-week treatment period) was statistically significant for both BRV treatment arms,” said the researchers.

EP0083 evaluated two BRV dosages as adjunctive treatment for FOS with or without secondary generalization despite current treatment with 1 or 2 permitted concomitant antiseizure medications (ASM). After an 8-week baseline, 449 participants (mean age 34.5 years, 53.8 percent women) were randomized 1:1:1 to daily BRV 50 mg (BRV50), BRV 200 mg (BRV200), or placebo, and then entered a 12-week treatment period. [Epilepsia Open 2024;9:1007-1020]

The mean duration of epilepsy was 16.6 years and age at onset was 18.4 years. Nearly 30 percent of participants had no previous ASM (ie, ASM taken and discontinued at any time prior to study entry). Twenty-two percent had one previous ASM. The fractions of patients who had 2–4 previous ASM ranged between 7 and 14 percent, while 16 percent had ≥5.

At baseline, the median 28-day FOS frequency was similar across study arms (9.8, 9, and 7.8 for placebo, BRV50, and BRV200, respectively). During the treatment period, these dropped to 7.2, 5.9, and 4.2, respectively.

The percent reductions in 28-day adjusted FOS frequency with BRV50 and BRV200 were 24.5 percent and 33.4 percent, respectively, as opposed to placebo (p=0.0005 and p<0.0001).

The 50-percent responder rate for FOS frequency was higher with BRV vs placebo (41.1 percent [BRV50] and 49.3 percent [BRV200] vs 19 percent). Comparisons between the BRV and placebo arms yielded odds ratios of 3.079 and 4.217 for BRV50 and BRV200 (p<0.0001 for both).

Compared with placebo, median percent reduction in FOS frequency from baseline over the 12-week treatment period was also greater with BRV50 (38.9 vs 21.3 percent; p=0.0011), more so with BRV200 (46.7 percent vs 21.3 percent; p<0.0001).

During the treatment phase, seven patients on BRV50 were classified as seizure-free (all seizure types). With BRV200, the corresponding number was 10. None in the placebo arm were seizure-free. Comparisons between the BRV and placebo arms yielded p-values of p=0.0146 (BRV50) and p=0.0017 (BRV200).

Safety profile

There were similar rates of treatment-emergent adverse events (TEAEs) across treatment arms (57, 60.1, and 58.4 percent for BRV50, BRV200, and placebo, respectively) and rates of discontinuation due to TEAEs were low (2.6, 3.4, and 4.7 percent, respectively). The most common TEAES tied to BRV were somnolence (14.4 percent) and dizziness (12.7 percent). According to the researchers, the similar rates imply that patients can start BRV treatment at therapeutic doses.

Of note, 5.4 percent of BRV-treated patients reported psychiatric TEAEs, the most common being insomnia (1.7 percent) and depression (1 percent). One BRV recipient reported TEAEs of suicidal ideation, while five discontinued due to psychiatric TEAEs (depression, irritability, postictal psychosis, and suicidal ideation).

“Most of the psychiatric and mental status findings that occurred in any treatment arm during the treatment period were also present at baseline,” the researchers noted.

Current ASM do not guarantee seizure-free status

Up to 30 percent of patients with epilepsy cannot achieve seizure freedom with currently available ASM. [JAMA 2022;327:1269-1281; https://www.who.int/publications/i/item/epilepsy-a-public-health-imperative, accessed September 6, 2024] “Lack of tolerability of an ASM can be a driver for nonadherence, which may lead to breakthrough seizures,” the investigators noted.

The findings from EP0083 add to the growing body of evidence, including long-term follow-up and real-world studies, that have reported the efficacy, safety, and tolerability of adjunctive BRV for FOS. [Epilepsia 2015;56:1890-1898; Epilepsy Res 2021;170:106526; Epilepsia 2020;61:636-646; CNS Drugs 2021;35:1289-1301; CNS Drugs 2023;37:819-835]

“[Taken together, our study shows that] adjunctive BRV was efficacious and well tolerated in adult Asian patients with FOS. Efficacy and safety profiles were consistent with BRV studies in predominantly non-Asian populations,” the researchers concluded.