Well-Established Safety Across Multiple Trials

Most common adverse reactions^* were lower in patients taking APTIOM without carbamazepine initiating at 400 mg¹

Study design

Common adverse reactions

ADVERSE REACTIONS IN ADULT ADJUNCTIVE THERAPY STUDIES

• Some adverse reactions occur more frequently when patients take APTIOM adjunctively with carbamazepine²
• Dosage modifications of both APTIOM and carbamazepine should be considered if these drugs are used concomitantly²

*Occurring in ≥4% of APTIOM-treated patients and ≥2% greater than placebo.²

^†Includes all APTIOM dose-initiation groups and concomitant ASMs in placebo-controlled adjunctive epilepsy studies.²

Aggression, agitation, & psychiatric

Incidences of aggression-related* and psychiatric^† ARs were comparable to placebo

IN ADULT ADJUNCTIVE THERAPY STUDIES¹

MOST COMMON AGGRESSION-RELATED AND PSYCHIATRIC ADVERSE REACTIONS IN ADULT ADJUNCTIVE THERAPY STUDIES

*Defined as events occurring in the Standardised MedDRA Queries of hostility/aggression.

^†Defined as events occurring in the System Organization Class of psychiatric disorders. Depression and suicidality-related treatment-emergent adverse events were reported more frequently in patients taking APTIOM than in the placebo group.²

^‡Includes APTIOM 400 mg, 800 mg, and 1200 mg.

Cognitive

Less than 2% of patients experienced any one cognitive dysfunction–related AR

IN ADULT ADJUNCTIVE THERAPY STUDIES¹

• Dose-dependent cognitive dysfunction–related adverse reactions were reported in 1% of placebo patients, 4% of patients on APTIOM 800 mg, and 7% of patients on APTIOM 1200 mg in controlled adult adjunctive epilepsy studies²
• Cognitive dysfunction–related adverse reactions were also observed in adult monotherapy studies²

Differences in incidence of adverse reactions by study phase¹

Study design

MOST COMMON* ADVERSE REACTIONS IN 18-WEEK, DOSE-BLINDED ADULT MONOTHERAPY STUDIES

1200 mg

1600 mg

These monotherapy studies did not include a placebo control group; therefore, causality could not be established.¹

Adverse reactions observed in these studies were generally similar to those observed and attributed to drug in adjunctive placebo-controlled studies.²

^*Adverse reactions occurring in the 8-week titration and taper phase and 10-week monotherapy phase (>5% of patients in either dose group).¹

^†Defined as 2 weeks of APTIOM titration plus 6 weeks of baseline ASM withdrawal.¹

^‡Defined as 10 weeks of monotherapy following baseline ASM withdrawal.¹

Safety data in pediatric patients 4 to 17 years of age²

Study design

Most common adverse reactions

RESULTS FROM 2 PLACEBO-CONTROLLED PEDIATRIC ADJUNCTIVE THERAPY STUDIES

• The most common baseline ASMs administered with APTIOM or placebo in controlled pediatric adjunctive epilepsy studies were valproic acid (all forms), carbamazepine, lamotrigine, topiramate, and levetiracetam¹
• Adverse reactions in pediatric patients are similar to those seen in adult patients²

*Occurring in ≥4% of APTIOM-treated patients and ≥2% greater than placebo.²

Psychiatric adverse reactions

Most common psychiatric adverse reactions^* in pediatric adjunctive therapy studies²

^*Defined as events occurring in the System Organization Class of psychiatric disorders.²

PSYCHIATRIC ADVERSE REACTIONS^† IN UNCONTROLLED 1-YEAR OPEN-LABEL EXTENSIONS OF THE PEDIATRIC ADJUNCTIVE THERAPY STUDIES

• Incidences of individual serious adverse reactions and psychiatric adverse reactions leading to discontinuation¹

^†Defined as events occurring in the System Organization Class of psychiatric disorders.¹

Cognitive dysfunction–related adverse reactions

COGNITIVE DYSFUNCTION–RELATED ADVERSE REACTIONS IN PEDIATRIC ADJUNCTIVE THERAPY STUDIES

Completion & discontinuation rates

APTIOM USE IN PEDIATRIC PATIENTS ACROSS CLINICAL STUDIES AS ADJUNCTIVE THERAPY

• After completing the double-blind portion of adjunctive therapy in the controlled studies, patients were optionally enrolled in the open-label extension phases¹
• 6% of APTIOM patients (n=202) discontinued treatment in the placebo-controlled pediatric adjunctive epilepsy studies as a result of any adverse reaction vs 3% of patients receiving placebo (n=160)¹
  - The adverse reactions that most commonly led to discontinuation (incidence ≥1% of APTIOM-treated patients) were allergic dermatitis and edema¹

DISCONTINUATION RATES

• The adverse reactions most commonly (>1% in APTIOM treatment group and greater than placebo) leading to discontinuation were edema and allergic dermatitis