START AND STAY WITH BRIVIACT FOR
PEDIATRIC PATIENTS

Available for patients as young as 1 month of age1

BRIVIACT® (brivaracetam) CV is indicated for the treatment of partial-onset seizures in patients 1 month of age and older.1

Available in multiple formulations with no required titration1

Examples of Oral and IV Administrations of BRIVIACT® Examples of Oral and IV Administrations of BRIVIACT®

Products not shown at actual size.

BRIVIACT injection may be used when oral administration is temporarily not feasible.1

RETENTION

One year after starting treatment, an estimated 7 in 10 pediatric patients remained on BRIVIACT2

KAPLAN-MEIER ESTIMATE OF PERCENTAGE OF PEDIATRIC PATIENTS WITH FOCAL SEIZURES (N=168) REMAINING ON TREATMENT IN A POOLED STUDY2


Percentage Of Patients with Focal Seizures Remaining On Treatment Over 24 Months, Kaplan-Meier Pediatrics Estimate, Graph

*Kaplan-Meier estimates of the percentage of subjects completing only the specified duration of treatment with BRIVIACT regardless of any discontinuation reason.2

 

This long-term retention data is an estimation of how long patients have remained on treatment in select BRIVIACT clinical studies. Conclusions of long-term efficacy or safety should not be drawn based on this data.

Two years after starting treatment, an estimated 6 in 10 pediatric patients remained on BRIVIACT2

Study design2,3

  • Pooled data from Phase 2a and Phase 3a open-label trials of BRIVIACT
  • Patients aged ≥1 month to <17 years (N=219), uncontrolled by 1-3 prior ASMs
  • Out of 219 patients, 168 had focal seizures
  • After dose adjustment, patients received BRIVIACT 1 to 5 mg/kg/day (maximum 200 mg/day)

EFFICACY

BRIVIACT efficacy extrapolated for pediatric patients1

Efficacy in adults was established without a titration period1

Adult efficacy data

Adult pivotal trial design1

  • Effectiveness was established in 3 fixed-dose, randomized, double-blind, placebo-controlled, multicenter studies, which included 1550 adult patients
  • Enrolled adult patients had focal seizures that were not adequately controlled by 1 to 2 concomitant AEDs
  • Patients taking concomitant levetiracetam were excluded from Study 3

AED=antiepileptic drug.

BRIVIACT efficacy was also studied in pediatric patients4

Pediatric study design4

  • Phase 2a, open-label, single-arm, fixed 3-step dose-escalation trial
  • Short-term safety and tolerability, pharmacokinetics, preliminary efficacy of BRIVIACT oral solution. Efficacy analyses were exploratory
  • Pediatric patients 1 month to <16 years of age
  • 1-week baseline period, 3-week evaluation period
 

Additional study design

  • In the treatment period, BRIVIACT oral solution dosage was divided into 2 daily doses and increased each week to approximately 0.8, 1.6, and 3.2 mg/kg/day for patients aged ≥8 years, and 1.0, 2.0, and 4.0 mg/kg/day for patients aged <8 years4
  • 99 patients were enrolled in the trial; 52 patients with focal seizures were included in the safety analysis, and 50 were included in the efficacy analysis. Only those patients experiencing seizures in the one-week baseline period (n=37) were included in the seizure reduction and responder rate analyses. All 50 focal seizure patients were included in the seizure freedom analysis4

Demographic data

BRIVIACT was studied in a challenging pediatric population with focal seizures1,4

 

Pediatric trial results4

EFFICACY WAS EVALUATED OVER A 3‑WEEK PERIOD

30%

OF PATIENTS

experienced a ≥50%
reduction in seizure
days from baseline†

Based on treatment responses
seen in patients with focal
seizures (11/37; <16 years old).

24%

OF PATIENTS

achieved complete
seizure freedom over
a 3-week period‡

As seen in patients (12/50) with
focal seizures.

†Patients without seizure in baseline were excluded. Number of seizure days standardized to a 28-day duration.

‡With or without secondary generalization and no primary generalized seizures at baseline.

SAFETY

In adult adjunctive trials, most adverse events with BRIVIACT were reported to be mild or moderate2

The safety profile of BRIVIACT was established in adults in phase 3 placebo-controlled trials1

Most common adverse reactions in adults

Most common adverse reactions that occurred in ≥5% for BRIVIACT
and at least 2% more frequently than placebo1

The safety profile for pediatric patients was
similar to adults1

  • BRIVIACT has been shown to be generally well tolerated for infants
    1 month of age and older2

The most common drug-related treatment-emergent adverse events (TEAEs) in pooled pediatric studies (≥5%)2

Common Pediatric Adverse Reactions, Table

Phase 2a and phase 3a
open-label study design

STUDY DESIGN:
Pooled safety data from phase 2a and phase 3a open-label trials of BRIVIACT in patients aged 1 month to <17 years (N=219), uncontrolled by 1 to 3 AEDs. Of the 219 patients, 168 had focal seizures. After dose adjustment, patients received BRIVIACT 1 to 5 mg/kg/day (maximum 200 mg/day).2,3

BRIVIACT injection safety and tolerability is consistent with oral formulations1

  • The safety and tolerability of BRIVIACT IV has been evaluated as a 15-minute infusion or a bolus (up to 2-minute) injection in an open-label study in children aged 2 months to <16 years with epilepsy1,2
  • The safety and pharmacokinetics of BRIVIACT were similar in the infusion and bolus injection groups2
  • Adverse reactions with BRIVIACT injection in adult and pediatric patients were generally similar to those observed with BRIVIACT tablets. Other adverse events that occurred in adult patients who received BRIVIACT injection included dysgeusia, euphoric mood, feeling drunk, and infusion site pain1

BEHAVIOR & CONDITION

Behavioral and cognitive stability with BRIVIACT: Pediatric measures were generally unchanged from baseline2

Based on 2 established neurological measurement tools5,6

  • Parents or caregivers completed the BRIEF® and Achenbach Child Behavior Checklist (CBCL) surveys at regular intervals during the long-term, phase 3a, follow-up study. The version appropriate for the patient’s age at each visit was completed2,3

Study design2,3

Study design for evaluating BRIEF® and Achenbach CBCL

  • Pooled interim analysis from phase 2a and phase 3a open-label trials
  • Included pediatric patients 1 month to <17 years (N=219) uncontrolled by 1 to 3 AEDs
  • Of the 219 patients, 168 had focal seizures
  • Parents or caregivers completed the BRIEF® and Achenbach CBCL surveys at regular intervals during the long-term, phase 3a, follow-up study. The version appropriate for the patient’s age at each visit was completed
  • AED changes were permitted over the duration of the long-term follow-up study
  • Additional factors may influence measures of behavior and cognition

Executive function and self-regulation categories§ remained stable for the majority of school-aged children (aged 5 to ≤17 years), relative to baseline2

 

BRIEF® GLOBAL EXECUTIVE COMPOSITE SCORE CATEGORY CHANGES (N=92)2§

Percentage of Patients Who Worsened, Improved, or Had No Change in Category, Graph

§T-score categories were defined as “normal” (0 to <50), “borderline” (50 to <65), and “clinically significant” (≥65).

BRIEF=Behavior Rating Inventory of Executive Function.

Emotional, behavioral, and social problem categoriesII remained stable among the majority of school-aged children (aged 6 to <17 years), relative to baseline2

 

SHIFT IN CHILD BEHAVIOR CHECKLIST T-SCORE CATEGORIES (N=127)II

A similar trend was observed among patients aged 1½ months to 5 years who were assessed by a separate CBCL.

PSYCHIATRIC ADVERSE REACTIONS: BRIVIACT causes psychiatric adverse reactions, including non-psychotic and psychotic symptoms. These events were reported in approximately 13% of adult patients taking at least 50 mg per day of BRIVIACT compared to 8% of adult patients taking placebo. A total of 1.7% of adult patients taking BRIVIACT discontinued treatment due to psychiatric reactions compared to 1.3% of patients taking placebo. Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults. Advise patients to report these symptoms immediately to a healthcare provider.1

DOSING

A therapeutic dose on day 1 with the simplicity of no required titration1

For your pediatric patients with focal seizures, you can start with a therapeutic dose on day 1 with BRIVIACT and have room to adjust if needed based on clinical response and tolerability.

The recommended dosing regimen is dependent upon body weight for patients weighing less than 50 kg.

Recommended dosage



 

Multiple formulations for pediatric patients1

SIMPLE 1:1 DOSE CONVERSION

Examples of Oral and IV Administrations of BRIVIACT® Examples of Oral and IV Administrations of BRIVIACT®

Products not shown at actual size.

BRIVIACT oral solution and tablets1

Can be given with or without food

Tablets should be swallowed whole with liquid. They should not be chewed or crushed

No blood level, respiratory, or cardiac monitoring required

Intravenous injection only1

  • BRIVIACT injection may be used when oral administration is temporarily not feasible
  • BRIVIACT injection should be administered intravenously at the same dosage and same frequency as BRIVIACT tablets and oral solution
  • No refrigeration required
    • Can be stored in PyxisTM or Omnicell systems

BRIVIACT injection offers rapid administration

Median Tmax following a 2-minute bolus (administered undiluted) is <5 minutes7

Can be administered intravenously over 2 to 15 minutes1

No dilution required1


 
 
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UCB provides multiple resources for eligible patients starting on BRIVIACT

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Important Safety Information

WARNINGS AND PRECAUTIONS

  • Suicidal Behavior and Ideation: Antiepileptic drugs, including BRIVIACT, increase the risk of suicidal behavior and ideation. Monitor patients taking BRIVIACT for the emergence or worsening of depression; unusual changes in mood or behavior; or suicidal thoughts, behavior, or self-harm. Advise patients, their caregivers, and/or families to be alert for these behavioral changes and report them immediately to a healthcare provider.
  • Neurological Adverse Reactions: BRIVIACT causes somnolence, fatigue, dizziness, and disturbance in coordination. Somnolence and fatigue-related adverse reactions were reported in 25% of adult patients taking at least 50 mg per day of BRIVIACT compared to 14% of adult patients taking placebo. Dizziness and disturbance in gait and coordination were reported in 16% of adult patients taking at least 50 mg per day of BRIVIACT compared to 10% of adult patients taking placebo. The risk is greatest early in treatment but can occur at any time. Monitor patients for these signs and symptoms and advise them not to drive or operate machinery until they have gained sufficient experience on BRIVIACT.
  • Psychiatric Adverse Reactions: BRIVIACT causes psychiatric adverse reactions, including non-psychotic and psychotic symptoms. These events were reported in approximately 13% of adult patients taking at least 50 mg per day of BRIVIACT compared to 8% of adult patients taking placebo. A total of 1.7% of adult patients taking BRIVIACT discontinued treatment due to psychiatric reactions compared to 1.3% of patients taking placebo. Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults. Advise patients to report these symptoms immediately to a healthcare provider.
  • Hypersensitivity: BRIVIACT can cause hypersensitivity reactions. Bronchospasm and angioedema have been reported. Discontinue BRIVIACT if a patient develops a hypersensitivity reaction after treatment. BRIVIACT is contraindicated in patients with a prior hypersensitivity reaction to brivaracetam or any of the inactive ingredients.
  • Withdrawal of Antiepileptic Drugs: As with all antiepileptic drugs, BRIVIACT should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus.

DOSING CONSIDERATIONS

  • Dose adjustments are recommended for patients with all stages of hepatic impairment.
  • When BRIVIACT is co-administered with rifampin, an increase in the BRIVIACT dose is recommended.

ADVERSE REACTIONS

In adult adjunctive therapy placebo-controlled clinical trials, the most common adverse reactions (at least 5% for BRIVIACT and at least 2% more frequently than placebo) were somnolence and sedation, dizziness, fatigue, and nausea and vomiting symptoms. Adverse reactions reported in clinical studies of pediatric patients were generally similar to those in adult patients. Adverse reactions with BRIVIACT injection in adult and pediatric patients were generally similar to those observed with BRIVIACT tablets. Other adverse events that occurred in adult patients who received BRIVIACT injection included dysgeusia, euphoric mood, feeling drunk, and infusion site pain.  

BRIVIACT is a Schedule V controlled substance.

Please see full Prescribing Information

References

       
  1. BRIVIACT® (brivaracetam): US prescribing information. Smyrna, GA: UCB, Inc.
  2. Data on file. UCB, Inc.
  3. Patel AD, Badalamenti V, Gasalla T, Elmoufti S, Elshoff JP. Safety and tolerability of adjunctive brivaracetam in children with focal seizures: interim analysis of pooled data from two open-label trials. Eur J Paediatr Neurol. 2020;25:68-76. doi:10.1016/j.ejpn.2019.11.007
  4. Liu E, Dilley D, McDonough B, Stockis A, Daniels T. Safety and tolerability of adjunctive brivaracetam in pediatric patients <16 years with epilepsy: an open-label trial. Paediatr Drugs. 2019;21(4):291-301. doi:/10.1007/s40272-019-00332-y
  5. Gioia GA, Isquith PK, Retzlaff PD, Epsy KA. Confirmatory factor analysis of the Behavior Rating Inventory of Executive Function (BRIEF) in a clinical sample. Child Neuropsychol. 2002;8(4):249-257.
  6. Knepley MJ, Kendall PC, Carper MM. An analysis of the Child Behavior Checklist anxiety problems scale’s predictive capabilities. J Psychopathol Behav Assess. 2019;41(2):249-256. doi:10.1007/s10862-019-09722-5
  7. Stockis A, Hartstra J, Mollet M, Hadi S. Bioavailability and bioequivalence comparison of brivaracetam 10, 50, 75, and 100 mg tablets and 100 mg intravenous bolus. Epilepsia. 2016;57(8):1288-1293. doi:10.1111/epi.13433