INVEGA SUSTENNA - INVEGA TRINZA - INVEGA HAFYERA - Clinical Data in Black and/or African American Patients With Schizophrenia

SUMMARY

• A retrospective analysis evaluated the real-world data on relapses in adult Black and/or African American (AA) patients (n=592) diagnosed with schizophrenia who were adequately treated (AT) vs not adequately treated (NAT) with INVEGA SUSTENNA before transitioning to INVEGA TRINZA.¹
  • Relapse rates were significantly lower in AT vs NAT cohorts, 15.2% vs 23.0% in Black and/or AA population, and 18.8% vs 24.8% in overall population.
  • In AT vs NAT cohorts, the majority of relapses were reported in the mental health hospitalization category, 10.8% vs 16.9% in Black and/or AA population, and 14.8% vs 19.3% in overall population.
• A post hoc analysis of a phase 3, double-blind (DB), noninferiority study assessed the efficacy and safety of INVEGA HAFYERA vs INVEGA TRINZA long-acting injections (LAIs) for delaying time to relapse in a population of Black and/or AA patients (n=72) with schizophrenia.²
  • In the INVEGA HAFYERA vs INVEGA TRINZA groups, relapse rates were 10.2% vs 8.7% in Black and/or AA population, and 7.5% vs 4.9% in overall population.
  • In the INVEGA HAFYERA vs INVEGA TRINZA groups, treatment-emergent adverse events (TEAEs) were experienced by 71.4% (35/49) vs 73.9% (17/23) Black and/or AA patients and 62.1% (297/478) vs 58.5% (131/224) patients in the overall study.
• A post hoc analysis of the DREaM study assessed the effectiveness and safety of paliperidone palmitate (PP) vs oral antipsychotics (OAPs) in the Black and/or AA subset of patients (n=42).³
  • In the PP/PP vs OAP/OAP groups, 23.5% vs 44.0% of Black and/or AA patients experienced treatment failure (TF).
  • In the PP/PP (n=17) vs OAP/OAP (n=25) groups, 88.2% (15) vs 92.0% (23) patients experienced a TEAE. The most common TEAE in both groups was weight increase 52.9% (9) vs 44.0% (11).
• A post hoc analysis of the PRIDE study assessed the efficacy and safety of INVEGA SUSTENNA vs OAPs in Black and/or AA patients (n=275) with schizophrenia and a history of criminal justice system involvement.⁴
  • In the INVEGA SUSTENNA vs OAP groups, TF due to any event was 35.9% vs 52.3%.
  • In INVEGA SUSTENNA (n=145) vs OAP (n=130) groups, TEAEs reported in ≥10% of patients were injection site pain in 22.1% (32) vs 0% (0) patient, insomnia in 19.3% (28) vs  14.6% (19) patients, akathisia in 11.7% (17) vs 4.6% (6) patients, weight increase in 11.7% (17) vs 5.4% (7) patients, headache in 6.9% (10) vs 11.5% (15) patients, and dry mouth in 6.9% (10) vs 10.0% (13) patients.

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate can be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to mg of paliperidone palmitate to reflect the commercially available INVEGA SUSTENNA, INVEGA TRINZA, and INVEGA HAFYERA dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

• INVEGA SUSTENNA doses expressed as 39, 78, 117, 156, and 234 mg of paliperidone palmitate are equal to 25, 50, 75, 100, and 150 mg eq. of paliperidone, respectively.
• INVEGA TRINZA doses expressed as 273, 410, 546, and 819 mg of paliperidone palmitate are equal to 175, 263, 350, and 525 mg eq. of paliperidone, respectively.
• INVEGA HAFYERA doses expressed as 1,092 or 1,560 mg of paliperidone palmitate are equal to 700 and 1,000 mg eq. of paliperidone, respectively.

CLINICAL DATA

Bailey et al (2022)¹ conducted a retrospective analysis to evaluate real-world data on relapse in adult Black and/or AA patients (n=592) diagnosed with schizophrenia who were AT vs NAT with INVEGA SUSTENNA before transitioning to INVEGA TRINZA.

Study Design/Methods

• The retrospective analysis was conducted using data from June 2015 to December 2020 from the IBM^® MarketScan^® Multi-State Medicaid Database.
• Adult Black and/or AA patients with ≥1 claim for schizophrenia diagnosis before and/or at index date (ie, first INVEGA TRINZA prescription record) and continuous insurance plan enrollment for ≥12 months before and after index date were included.
• Patients with diagnosis of dementia and/or autism before index INVEGA TRINZA injection, clozapine use, and/or patients with dual eligibility (ie, Medicaid and Medicare) were excluded.
• Two primary INVEGA TRINZA cohorts were generated among Black and/or AA patients and the overall population using propensity score matching (PSM).
  • AT cohort included patients who were adequately treated with INVEGA SUSTENNA for ≥4 months (≥5 injections), wherein the last 2 INVEGA SUSTENNA doses were the same. The INVEGA TRINZA initiation dose was based on the previous INVEGA SUSTENNA dose.
  • NAT cohort included patients who received 0-2 doses of INVEGA SUSTENNA.
• Relapse was determined to have occurred if a patient had a claims record during the 2year follow-up period for mental health–related inpatient hospitalization, suicide attempt/self-inflicted harm/injury (undetermined intent), homicidal ideation, aggressive/violent behavior or hostility or incarceration.

Results

Baseline Characteristics

• After PSM, 1242 patients (AT and NAT, n=621 each) were included, of whom 592 patients were identified as Black and/or AA (AT and NAT, n=296 each).
• In the Black and/or AA population, 72.6% were male, and mean age was 37.6 years and 37.4 years in the AT and NAT cohorts, respectively.
• In the overall population, 72.1% were male, and mean age was 38.2 years and 38.0 years in the AT and NAT cohorts, respectively.

Efficacy

Relapse rates in AT vs NAT cohorts were 15.2% vs 23.0% (P=0.0135) in Black and/or AA population, and 18.8% vs 24.8% (P=0.0081) in overall population. In both populations, relapse rate was significantly lower in the AT cohorts compared with NAT cohorts.

There was 37% decrease in the risk of first relapse for the AT cohort compared with the NAT cohort in the Black and/or AA population (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.43-0.91). See Figure: Time to First Relapse in the Black and/or African American Population. In the overall population there was 28% decrease in the risk of first relapse for the AT cohort compared with the NAT cohort (HR, 0.72; 95% CI, 0.570.92). 

• The primary category for relapse in both populations was mental health hospitalization. See Table: Category of First Relapse in Both the Populations.

Johnston et al (2022)² conducted a post hoc analysis of a phase 3 (NCT03345342), DB, noninferiority study to assess the efficacy and safety of INVEGA HAFYERA vs INVEGA TRINZA in delaying time to relapse in Black and/or AA patients (n=72) with schizophrenia.

Study Design/Methods

• Patients included in the study were aged 18-70 years, with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) diagnosis of schizophrenia ≥6 months before screening and a Positive and Negative Syndrome Scale (PANSS) total score <70 at screening.
• Patients with DSM-V diagnosis other than schizophrenia, receipt of involuntary treatment, attempted suicide <12 months before screening and risk of suicide and violent behavior, or intolerability or severe reaction to moderate or higher doses of antipsychotic medication were excluded.
• The study design is described in Figure: Study Design.

Results

Baseline Characteristics

• The overall population (N=1036) included 158 patients who identified as Black and/or AA, of whom 72 were randomized in the DB phase (INVEGA HAFYERA, n=49; INVEGA TRINZA, n=23).
• In the Black and/or AA vs overall populations, the mean age was 45.7 years vs 40.8 years, and the male proportion was 70.8% vs 68.4%.

Efficacy

In the ITT population, relapse rates were low in DB phase. See Table: Reasons for Relapse at the End of 12 Months.

The difference (95% CI) between INVEGA HAFYERA and INVEGA TRINZA in patients remaining relapse-free was -1.2 (-17.3 to 14.9) in Black and/or AA patients and -2.9 (-6.8 to 1.1) in the overall population. Patients maintained clinical stability throughout the study; however, no clinically significant changes were observed in the PANSS (total and subscale) score and Clinical Global Impression-Severity (CGI-S) score between the treatment groups from DB baseline to the endpoint in the Black and/or AA as well as overall population.

Safety

In the INVEGA HAFYERA vs INVEGA TRINZA groups, TEAEs were experienced by 71.4% (35/49) vs 73.9% (17/23) Black and/or AA patients and 62.1% (297/478) vs 58.5% (131/224) patients in the overall population. No TEAE leading to death was reported in the Black and/or AA population; the incidence of TEAE-related death in overall patients in the INVEGA HAFYERA vs INVEGA TRINZA groups was 0.2% (1/478) vs 0.9% (2/224).

Starr et al (2021)³ conducted a post hoc analysis of DREaM (NCT02431702), a prospective, match-controlled, double-randomized, open-label, flexible-dose study assessing the effectiveness and safety of PP vs OAPs in the Black and/ or AA subset of patients (n=42).

Study Design/Methods

• Patients included in study were aged between 18 and 35 years, with a current diagnosis of schizophrenia and schizophreniform disorder, confirmed by structured clinical interview for DSM-V disorders, with first psychotic episode within the past 24 months.
• This post hoc analysis focuses on patients in extended disease progression (EDP) analysis. See Figure: DREaM Study Design.

Results

Baseline Characteristics

• In the EDP (ITT) analysis of DREaM, 42 Black and/or AA patients (PP/PP, 17; OAP, 25) were included.
• Mean age of patients was 23.0 years, and 69.0% were male.

Efficacy

In the Black and/or AA population, 23.5% vs 44.0% of patients experienced TF in the PP/PP vs OAP groups, resulting in a 55% reduction in TF in the PP vs OAP groups (HR, 0.45 [95% CI, 0.14-1.42]). The difference in time to first treatment failure was not statistically significant (P=0.165) due to the small sample size. See Figure: TtFTF (EDP ITT Analysis Set).

The most common reason for first treatment failure in the PP/PP treatment group was discontinuation of treatment due to safety or intolerability in 11.8% (2/17) patients, and the most common reasons for first treatment failure in the OAP treatment group were psychiatric hospitalization in 16.0% (4/25) patients and deliberate selfinjury or suicidal or homicidal ideation in 16.0% (4/25) patients.

Safety

See Table: Most common Treatment-Emergent Adverse Events and Serious Adverse Events in PP/PP vs OAP/OAP Treatment Groups.

Lynum et al (2021)⁴ conducted a post hoc analysis of PRIDE (NCT01157351), a randomized, prospective, open-label, event-monitoring, board-blinded, parallel-group, multicenter study to assess the efficacy and safety of INVEGA SUSTENNA vs OAPs in Black and/or AA patients with schizophrenia and a history of criminal justice system involvement.

Study Design/Methods

• Patients included in study were aged between 18 and 65 years, with a current diagnosis of schizophrenia (DSMIV), confirmed by Mini-International Neuropsychiatric Interview (MINI, version 6), and contact with the criminal justice system ≥2 times during the previous 2 years, with ≥1 of these events leading to incarceration.  
• Patients were excluded if they had used clozapine within 3 months of screening or had received an injectable antipsychotic within 2 injection cycles of screening.
• Patients were randomized (1:1) to receive INVEGA SUSTENNA or OAP after 2 weeks of the screening/washout period.

Results

Baseline Characteristics

• Overall, 444 patients (ITT population) were included in the PRIDE study, of whom 275 were identified as Black and/or AA (INVEGA SUSTENNA, n=145; OAP, n=130).
• In the INVEGA SUSTENNA vs OAP groups, mean age was 38.1 years vs 39.8 years and male proportion was 86.9% vs 87.7%.

Efficacy

In the INVEGA SUSTENNA vs OAP groups, TF due to any event was 35.9% vs 52.3%. The risk of first treatment failure was numerically higher in the OAP vs INVEGA SUSTENNA groups; however, the difference was not statistically significant (HR, 1.39; 95% CI, 0.97-1.99; P=0.075). The most common reason for first treatment failure in the INVEGA SUSTENNA vs OAP groups was institutionalization (psychiatric hospitalization or arrest/incarceration; 30.3% vs 47.7%). Significant delay in the first institutionalization was observed in the INVEGA SUSTENNA vs OAP groups (HR, 1.49; 95% CI, 1.01-2.19; P=0.043). See Table: Efficacy Outcomes in the INVEGA SUSTENNA vs OAP Treatment Groups.

Over a 15-month period, mean cumulative number of TFs due to any event or institutionalization was lower in the INVEGA SUSTENNA vs OAP groups; however, the difference was not statistically significant.

Safety

See Table: Treatment-Emergent Adverse Events in INVEGA SUSTENNA vs OAP Treatment Groups.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 18 June 2025.