Summary

• The efficacy and safety of INVEGA HAFYERA (paliperidone palmitate 6-month [PP6M]) for the treatment of schizophrenia in adult patients who had previously been stabilized on either INVEGA SUSTENNA^® (paliperidone palmitate 1-month [PP1M]) for at least 4 months or INVEGA TRINZA^® (paliperidone palmitate 3-month [PP3M]) for at least one 3-month injection cycle was evaluated in a phase 3, randomized, double-blind (DB), multicenter, non-inferiority study (N=702).¹
  • INVEGA HAFYERA demonstrated non-inferiority to INVEGA TRINZA on the primary endpoint of time to first relapse at the end of the 12-month DB phase in the intentto-treat (ITT) analysis.¹
  • In the ITT analysis, 7.5% of patients in the INVEGA HAFYERA treatment group and 4.9% of patients in the INVEGA TRINZA treatment group experienced a relapse event.¹
• A post-hoc analysis of the noninferiority study compared the efficacy and safety outcomes for patients who transitioned to INVEGA HAFYERA from INVEGA SUSTENNA (n=231) vs INVEGA TRINZA (n=247).²
  • Relapse occurred in 7.8% of patients in the PP1M/PP6M group and 7.3% in the PP3M/PP6M group.²
  • At least 1 or more treatment-emergent adverse events occurred for 61.0% of patients in the PP1M/PP6M group and 63.2% in the PP3M/PP6M group.²

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to milligrams of paliperidone palmitate to reflect the commercially available 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

Najarian et al (2022)¹ conducted a phase 3, randomized, DB, active-controlled, parallel-group, multicenter, noninferiority study to evaluate the efficacy and safety of INVEGA HAFYERA on time to first relapse in adults with schizophrenia who were previously stabilized on corresponding doses of INVEGA SUSTENNA or INVEGA TRINZA.

Primary Study Results

• A total of 702 patients were enrolled in the study. Baseline demographic characteristics in the ITT analysis were generally similar across the INVEGA HAFYERA and INVEGA TRINZA groups.¹
• INVEGA HAFYERA (n=478) demonstrated noninferority to INVEGA TRINZA (n=224) on the primary endpoint of time to first relapse at the end of the 12-month period in the ITT population.¹
  • In the ITT analysis, 36 patients (7.5%) in the INVEGA HAFYERA group and 11 patients (4.9%) in the INVEGA TRINZA group experienced a relapse event in the DB phase
  • Non-inferiority was defined as the lower limit of the 2-sided 95% CI of the difference in the relapse-free rates between PP3M and PP6M exceeding −10%
• The safety profile of INVEGA HAFYERA was generally consistent with previous studies of INVEGA SUSTENNA and INVEGA TRINZA¹
  • Most TEAEs were mild or moderate in severity. Serious TEAEs were mostly related to worsening of psychiatric symptoms; schizophrenia was the most frequent.
    • The most common TEAEs (≥5% rate) in either treatment arm were weight increased, injection-site pain, headache, upper respiratory tract infection, and nasopharyngitis
  • Four deaths were reported in the trial. Investigators considered these deaths as not related to study medication.

Post-Hoc Analysis Results

Patient Demographics

• A total of 231 patients in the PP1M/PP6M group, 247 patients in the PP3M/PP6M group, and 224 patients in the PP3M group were included in this analysis (See Table: Baseline Demographic Characteristics - Post-hoc Analysis).²

Efficacy Outcomes

• The Kaplan-Meier estimate of the treatment group difference (95% CI) versus PP3M was −2.7 (−8.5 to 3.0) in the PP1M/PP6M group and −2.9 (−8.3 to 2.4) in the PP3M/PP6M group.²
• Relapse occurred in 7.8% of patients in the PP1M/PP6M group and 7.3% in the PP3M/PP6M group; the difference (95% CI) in percentage of patients who were relapse free was 0.7 (−4.4, 5.8) (See Figure: Kaplan-Meier Plot of Patients Without Relapse - Post-hoc Analysis).²
  • The median time to relapse (the time at which the cumulative survival function equals 0.5 or 50%) was not estimable for any group because of the low number of relapses during the DB phase.
• The magnitudes of change from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between groups.²

Safety Outcomes

• Overall, 61.0%, 63.2%, and 58.5% of patients in the PP1M/PP6M, PP3M/PP6M, and PP3M groups, respectively, experienced ≥1 TEAE (See Table: Overall Summary of TEAEs – Post-hoc Analysis).²
  • Of these TEAEs, 5.2%, 4.9%, and 6.7% were considered serious in the PP1M/PP6M, PP3M/PP6M, and PP3M groups, respectively.
  • The most common TEAEs (occurring in ≥5% of patients) were weight increased, injection site pain, headache, nasopharyngitis and upper respiratory infection.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 19 August 2024.