First Real-World Study Finds Brivaracetam Sustained-Release (SR) Safe and Effective for Focal Seizures in Indian Population

The recently published BEAM study revealed that Brivaracetam (BRV) sustained-release (SR) tablets are safe and effective for the treatment of focal seizures in Indian real-life settings.

The study published in the January 2025 issue of Seizure: European Journal of Epilepsy provides the first Indian real-world evidence of BRV-SR's effectiveness and safety, highlighting its feasibility for managing focal epilepsy with good retention rates and improved Quality of Life (QoL).

Epilepsy, the fourth most common neurological disease globally, affects 50 million people, according to the World Health Organization (WHO). Anti-seizure medications (ASMs) are key to treatment, and sustained-release (SR) formulations improve compliance and convenience. Brivaracetam (BRV), a third-generation anti-seizure medication (ASM) with a short half-life, is ideal for SR use.

In 2023, the Central Drugs Standard Control Organization (CDSCO) approved BRV-SR tablets for partial-onset seizures in India. Researchers, thereafter conducted the first real-world study in India to assess its effectiveness and tolerability in focal-onset and secondary generalized seizures.

In this observational study, researchers analyzed data from 1,989 patients (mean age - 42.33±12.33 years) receiving BRV-SR at 181 centers. The primary endpoint was efficacy, measured by changes in seizure frequency. Secondary endpoints included responder rates (≥50% reduction in the frequency of focal-onset seizures [FoS] or focal-to-bilateral tonic-clonic seizures [FBTCS]), usage patterns, clinical global impression-efficacy index (CGI-EI), and safety outcomes, offering a comprehensive real-world evaluation of BRV-SR medication.

Among 1,989 patients, 44.7% had epilepsy for 0–1 year, 34.64% for 1–3 years, 15.69% for 3–5 years, and 4.97% for over 5 years. Psychiatric comorbidities included depression (21.97%), sleep disturbance (15.54%), and anxiety (9.6%), while 58.27% of patients had no psychiatric issues. Previously prescribed ASMs included levetiracetam (21.62%), valproate (20.01%), lacosamide (14.08%), oxcarbazepine (12.57%), carbamazepine (9.05%), lamotrigine (6.28%), perampanel (2.82%) and brivaracetam IR (0.25%) at baseline.

The key findings from the study are:

Primary Endpoints:

• The median baseline frequency of FoS and FBTCS was 2 per month, which decreased to 1 per month after BRV-SR treatment, showing a 50% reduction. (Fig.1)

Fig.1. Effectiveness of BRV-SR for the overall population. (A) Median percentage reduction from baseline in FOS/FBTCS frequency, (B) 50% responder rate, and (C) Complete seizure freedom (%). BRV, brivaracetam; SR, sustained-release; FOS, focal-onset seizures; FBTCS, focal to bilateral tonic-clonic seizures.

Secondary Endpoints:

• Responder Rate and Seizure Freedom: A 50% or greater reduction in seizure frequency (responder rate) was achieved by 72.1% of patients. (Fig.1) Complete seizure freedom was reported in 1268 (63.75%) of patients overall, with similar rates across BRV-SR doses of 50 mg (63.16%), 100 mg (64.01%), and 200 mg (63.57%).
• Clinical Global Impression-Efficacy Index (CGI-EI Ratings): Among 1,895 patients with available CGI-EI rating data, BRV-SR showed "marked improvement" in 1310 (69.14%), "moderate improvement" in 452(23.85%), "minimal improvement" in 131 (6.91%), and “unchanged” in 2 (0.1%) patients. Improvements were consistent across BRV-SR doses of 50 mg, 100 mg, and 200 mg/day.

Subgroup Analysis of Clinical Importance:

• Effectiveness by Seizure Type: Patients with focal-onset seizures (FoS) had a 71.44% responder rate (≥50% seizure reduction) and 63.34% seizure freedom, while those with focal-to-bilateral tonic-clonic seizures (FBTCS) showed a 73.42% responder rate and 64.79% seizure freedom, with no significant differences between the groups.
• Effectiveness by Epilepsy Duration: Patients with epilepsy >1 year showed better outcomes, with a 77.64% responder rate and 66% seizure freedom, compared to 65.24% and 60.96% in those with ≤ 1-year duration
• Monotherapy vs. Adjunctive Therapy: BRV-SR as adjunctive therapy resulted in higher responder rates (80.58% vs. 57.87%) and seizure freedom (68.22% vs. 56.26%) compared to monotherapy.
• Correlation of ASM-Induced BAEs and BRV-SR Initiation: Patients with ASM-induced behavioral adverse events (BAEs) were more likely to be prescribed BRV-SR, indicating it is preferred for managing intolerable side effects of other ASMs.
• Psychiatric Comorbidities: BRV-SR was significantly associated with use in patients with psychiatric comorbidities.
• Drug-Resistant Epilepsy: BRV-SR was also found to be effective in drug-resistant epilepsy cases.

Safety Analysis:

• 52 patients (2.61%) reported mild and transient adverse events (AEs), including somnolence/sedation (0.9%), dizziness (0.8%), fatigue (0.5%), and nausea/vomiting (0.4%). No serious AEs requiring treatment withdrawal were observed with BRV-SR tablets.

The BEAM study highlights Brivaracetam Sustained-Release (BRV-SR) as a well-tolerated, effective, and easy-to-use treatment for focal epilepsy in the Indian population, demonstrating significant seizure reduction, high response rates, and improved quality of life.

Reference:

1) Ranganathan, L. N., Kulkarni, G., Kakkad, A., Korukonda, K., & Chouksey, N. (2025). First clinical post-approval, observational study to assess clinical safety and effectiveness of brivaracetam sustained-release formulation in real-life settings of India: BEAM study. Seizure: European Journal of Epilepsy, 125, 132–139.