Short-term: Two 6-week, pivotal trials evaluated efficacy and safety in patients with schizophrenia (SZ) who would benefit from hospitalization

REXULTI pivotal trial design^1,2:

• Two 6-week, randomized, placebo-controlled, fixed-dose pivotal trials conducted in patients who met DSM-IV-TR criteria for SZ and would benefit from hospitalization or continued hospitalization for an acute exacerbation of symptoms
• Treatment initiated at 1 mg/day on Days 1–4, titrated to 2 mg/day on Days 5–7, then maintained or increased to 4 mg/day on Day 8, depending on treatment arm
• Primary endpoint was change in total PANSS score from baseline to 6 weeks

Patient demographic—average baseline PANSS total score: moderately to markedly ill

Study 3 and Study 4: REXULTI—mean baseline
PANSS total score at randomization^3,4,a

The PANSS is a 30-item scale that measures positive symptoms of SZ (7 items), negative symptoms of SZ (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); the total PANSS scores range from 30 (best) to 210 (worst).

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^aPatients were hospitalized for screening and throughout the 6-week treatment phase.²

^bMean baseline PANSS total scores (SD) for patients were Study 3: REXULTI 2 mg/day, 95.9 (13.8); REXULTI 4 mg/day, 94.7 (12.1); placebo, 95.7 (11.5); Study 4: REXULTI 2 mg/day, 96.3 (12.9); REXULTI 4 mg/day, 95.0 (12.4); placebo, 94.6 (12.8).

^cn=358; sum of patients in the efficacy analyses who received placebo in Study 3 and Study 4.

^dn=718; sum of patients in the efficacy analyses who received REXULTI 2 mg/day or 4 mg/day in Study 3 and Study 4.

Short-term data: 20-point reduction in PANSS total score from baseline with REXULTI 4 mg across 2 trials

Study 3 and Study 4: REXULTI 4 mg/day—
reduction in PANSS total score
vs placebo in pooled data at 6 weeks⁵

Study 3 and Study 4: REXULTI 4 mg/day—reduction
in PANSS total score vs placebo in pooled data at 6 weeks⁵

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^ep<0.0001 vs placebo.⁵

Adapted with permission.

Difference in mean reduction in PANSS total score vs placebo at Week 6 in both pivotal trials

Study 3¹

Study 4²

• Statistical significance was achieved at 2 mg/day vs placebo in Study 3¹
• A 1-mg/day treatment arm was included in Study 4. Statistical significance was not achieved for the primary endpoint with either the 1-mg/day dose or the 2-mg/day dose compared with placebo (p>0.05)²

The PANSS is a 30-item scale that measures positive symptoms of SZ (7 items), negative symptoms of SZ (7 items), and general psychopathology (16 items), with each rated on a scale of 1 (absent) to 7 (extreme); the total PANSS scores range from 30 (best) to 210 (worst).

CI, confidence interval; LS, least squares.

Contraindication:

In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

Maintenance: PANSS total score during stabilization and maintenance phases

Study 5 trial design: REXULTI—PANSS total score during stabilization
and maintenance phases for REXULTI 1 mg/day to 4 mg/day and placebo^6,7

Single-blind stabilization^f

Patients with SZ were stabilized on flexible doses of REXULTI 1 mg/day to 4 mg/day for at least 12 consecutive weeks

Double-blind maintenance

Patients who met stabilization^f criteria and remained on a stable dose of REXULTI for at least the last 4 weeks were then randomized 1:1 for 52 weeks to either:

• Their achieved stable dose of REXULTI 1 mg/day to 4 mg/day
• Placebo

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PANSS total mean baseline scores [SD] (at Week 0 in the maintenance phase): REXULTI 1 mg/day to 4 mg/day (n=97), 56.5 [8.7]; placebo (n=105), 58.1 [8.1].⁶

Patients had a PANSS total score of >80 and, if needed, were part of a 1- to 4-week washout phase of previous medications before moving on to stabilization.

^fStabilization was defined as all of the following: (1) outpatient status; (2) PANSS total score ≤70; (3) a PANSS score of ≤4 on conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content; (4) CGI-severity ≤4; (5) no current suicidal behavior; (6) no violent or aggressive behavior resulting in injury or property damage.⁶

The PANSS is a 30-item scale that measures positive symptoms of SZ (7 items), negative symptoms of SZ (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); the total PANSS scores range from 30 (best) to 210 (worst).

CGI, Clinical Global Impressions; PANSS, Positive and Negative Syndrome Scale; SD, standard deviation.

Important Warning and Precaution for Cerebrovascular Adverse Events, Including Stroke:

In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Demonstrated efficacy as maintenance treatment

• Mean dose during maintenance phase was 3.6 mg/day⁶
• Primary endpoint was time from randomization to impending relapse in the maintenance phase
  • Impending relapse was defined as any of the following:
    1. CGI-improvement score of ≥5 and an increase to >4 on PANSS conceptual disorganization, hallucinatory behavior, suspiciousness, or unusual thought content, with either a ≥2 increase on a specific item or ≥4 increase on the combined 4 items
    2. Hospitalization due to worsening of psychotic symptoms
    3. Current suicidal behavior
    4. Violent/aggressive behavior

• The risk of impending relapse was calculated using a Kaplan-Meier estimation over the 52 weeks. The calculated hazard ratio (HR=0.292 [95% CI: 0.156, 0.548], p<0.0001) was used to estimate the reduction in risk of impending relapse for patients continuing treatment with REXULTI vs those given placebo⁶
• Trial was terminated early because maintenance of efficacy had been demonstrated

Important Warning and Precaution for Neuroleptic Malignant Syndrome (NMS):

NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs including REXULTI. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of REXULTI, intensive symptomatic treatment, and monitoring.