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INVEGA HAFYERA®

(paliperidone palmitate 6-month)

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INVEGA HAFYERA® (paliperidone palmitate 6-month)
Medical Information

INVEGA HAFYERA – Conversion from INVEGA SUSTENNA vs INVEGA TRINZA

Last Updated: 07/17/2026

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, noninferiority study (N=702).1
    • INVEGA HAFYERA demonstrated noninferiority 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
    • Median time to relapse was not estimable due to the low number of relapses during the DB phase.
    • Relapse occurred in 7.8% of patients in the INVEGA SUSTENNA/INVEGA HAFYERA group and 7.3% in the INVEGA TRINZA/INVEGA HAFYERA group.2
    • During the DB phase, at least 1 or more treatment-emergent adverse events (TEAEs) occurred for 61.0% of patients in the INVEGA SUSTENNA/INVEGA HAFYERA group and 63.2% in the INVEGA TRINZA/INVEGA HAFYERA group.2
  • A multicenter, observational, ambispective mirror-image longitudinal study evaluated the 12-month effectiveness and safety of INVEGA HAFYERA in patients with schizophrenia who were previously stabilized on INVEGA SUSTENNA or INVEGA TRINZA in real‑world clinical settings.3
    • The proportion of patients requiring hospitalization decreased significantly at both
      6 months (P<0.01) and 12 months (P<0.05) compared with the year prior to treatment initiation.3
    • The mean Clinical Global Impression (CGI) score decreased significantly, from 4.1 at baseline to 3.8 at 6 months (P<0.01) and 3.7 at 12 months (P<0.001).3
    • The Sheehan Disability Scale (SDS) score decreased from 29.0 at baseline to 26.7 at 6 months (P<0.001) and 26.5 at 12 months (P<0.001).3
    • During the follow-up period, TEAEs were reported in 32.6% of patients at 6 months and 38.2% at 12 months (≥1 AE). Dyslipidemia (75.0% at 6 months and 82.1% at 12 months) and parkinsonism(38.3% at 6 months and 46.8% at 12 months) were the commonly reported AEs.3

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.

Study Design1A screenshot of a computer screen AI-generated content may be incorrect.

Abbreviations: CGI-S, Clinical Global Impression-Severity; D, deltoid; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, fifth edition; G, gluteal; NMS, neuroleptic malignant syndrome; PANSS, Positive and Negative Syndrome Scale; PP1M, paliperidone palmitate 1-month; PP3M, paliperidone palmitate 3-month; PP6M, paliperidone palmitate 6-month; PSP, Personal and Social Performance; R, randomization; TD, tardive dyskinesia.
aPatients had to be on the same dosage strength and frequency for 3 injection cycles before screening.
bPatients received doses of PP6M on day 1 in the left gluteal muscle and on day 183 in the right gluteal muscle, while receiving a placebo on day 92 in the right gluteal muscle and on day 274 in the left gluteal muscle.
cThe dose level and number of injections depend on the previous treatment and individual efficacy and tolerability results.
dOpen-label transition and maintenance, n=838.
eDose matched by straightforward progression or established conversion, per the dose received during screening or transition, as applicable.
fTotal PANSS score was required to be <70 to enter the double-blind treatment period. Randomization occurred on the day of first double-blind injection, 1 and 3 months after the maintenance injection of PP1M and PP3M, respectively.
gAfter randomization, for 2 consecutive assessments separated by 3-7 days.

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 noninferiority 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
    • Noninferiority was defined as the lower limit of the 2-sided 95% CI of the difference in the relapse-free rates between INVEGA TRINZA and INVEGA HAFYERA 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

Correll et al (2025)2 conducted a post hoc analysis of the phase 3 noninferiority trial1 to assess the efficacy and safety of patients who appropriately transitioned to INVEGA HAFYERA from INVEGA SUSTENNA and those who transitioned to INVEGA HAFYERA from INVEGA TRINZA.

Results

Patient Demographics

Baseline Demographic Characteristics - Post hoc Analysis2
INVEGA SUSTENNA/
INVEGA HAFYERA
(n=231)
INVEGA TRINZA/
INVEGA HAFYERA
(n=247)
INVEGA TRINZA
(n=224)
Age,a years, mean (SD)
39.4 (11.91)
42.8 (11.42)
40.0 (10.98)
Age at schizophrenia diagnosis, years, mean (SD)
28.0 (9.11)
27.4 (8.93)
27.5 (9.05)
Duration of illness, years,
mean (SD)
11.4 (9.89)
15.5 (10.71)
12.5 (9.84)
Male, n (%)
148 (64.1)
178 (72.1)
154 (68.8)
Baseline BMI, mean (SD), kg/m2
26.9 (4.79)
28.8 (4.96)
27.5 (4.96)
Abbreviations: BMI, body mass index; SD, standard deviation.
aAge at screening.
Efficacy Outcomes
  • The Kaplan-Meier estimate of the treatment group difference (95% CI) in the percentage of patients who remained relapse-free versus INVEGA TRINZA was −2.7%
    (−8.5 to 3.0) in the INVEGA SUSTENNA/INVEGA HAFYERA group and −2.9% (−8.3 to 2.4) in the INVEGA TRINZA/INVEGA HAFYERA group.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 mean change from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between groups (See Table: Mean Change From Baseline in PANSS, CGI-S, and PSP During the DB Phase).2

Kaplan-Meier Plot of Patients Without Relapse - Post Hoc Analysis2

A graph with numbers and a line AI-generated content may be incorrect.

Abbreviations: DB, double-blind; PP1M, paliperidone palmitate once-monthly; PP3M, paliperidone palmitate once-every-3-months; PP6M, paliperidone palmitate once-every-6-months.


Mean Change From Baseline in PANSS, CGI-S, and PSP During the DB Phase2
INVEGA SUSTENNA/
INVEGA HAFYERA
(n=231)
INVEGA TRINZA/
INVEGA HAFYERA
(n=247)
INVEGA TRINZA
(n=224)
PANSS total score
   Mean at DB baseline
   (SD)
53.3 (9.52)
50.6 (9.51)
51.4 (9.77)
   Mean change from
   baseline (SD)
−1.8 (9.74)
−1.8 (8.11)
−1.6 (7.40)
Mean PANSS subscale scores (SD)
   Positive subscale
      Baseline (DB)
11.3 (3.36)
10.7 (3.05)
10.8 (2.98)
      Change from
      baseline
−0.1 (3.54)
−0.2 (3.06)
−0.1 (2.82)
   Negative subscale
      Baseline (DB)
16.3 (4.06)
15.8 (4.32)
15.9 (4.18)
      Change from
      baseline
−0.8 (2.85)
−0.6 (2.54)
−0.6 (2.61)
CGI-S scorea
   Mean at DB baseline
   (SD)
3.0 (0.76)
3.0 (0.80)
3.0 (0.77)
   Mean change from
   baseline (SD)
0.0 (0.77)
0.0 (0.63)
0.0 (0.63)
PSP scoreb
   Mean at DB baseline
   (SD)
66.5 (11.15)
66.2 (13.67)
66.5 (11.82)
   Mean change from
   baseline (SD)
1.1 (7.31)
0.9 (6.94)
1.1 (8.11)
aINVEGA SUSTENNA/INVEGA HAFYERA, n=228; INVEGA TRINZA/INVEGA HAFYERA, n=245; INVEGA TRINZA, n=220.
bINVEGA SUSTENNA/INVEGA HAFYERA, n=229; INVEGA TRINZA/INVEGA HAFYERA, n=246; INVEGA TRINZA, n=221.
Abbreviations: CGI-S, Clinical Global Impression-Severity scale; DB, double-blind; PANSS, Positive and Negative Syndrome Scale; PSP, Personal and social performance scale.
Safety Outcomes
  • During the DB phase, 61.0%, 63.2%, and 58.5% of patients in the INVEGA SUSTENNA/INVEGA HAFYERA, INVEGA TRINZA/INVEGA HAFYERA, and INVEGA TRINZA groups, respectively, experienced ≥1 TEAE (See Table: Overall Summary of TEAEs - Post Hoc Analysis).2
    • The most common TEAEs (occurring in ≥5% of patients) were weight increased, injection site pain, headache, nasopharyngitis and upper respiratory infection
  • Of these TEAEs, 5.2%, 4.9%, and 6.7% were considered serious in the INVEGA SUSTENNA/INVEGA HAFYERA, INVEGA TRINZA/INVEGA HAFYERA, and INVEGA TRINZA groups, respectively.
    • TEAEs leading to withdrawal and death were reported in 2.6% and 0.4% of patients in the INVEGA SUSTENNA/INVEGA HAFYERA group, 4.0% and 0% in the INVEGA TRINZA/INVEGA HAFYERA group, and 2.7% and 0.9% in the INVEGA TRINZA group, respectively.

Overall Summary of TEAEs - Post Hoc Analysis2
Number of Patients (%)
INVEGA SUSTENNA/ INVEGA HAFYERA (n=231)
INVEGA TRINZA/ INVEGA HAFYERA
(n=247)
INVEGA TRINZA
(n=224)
≥1 TEAEs
141 (61.0)
156 (63.2)
131 (58.5)
≥1 serious TEAEs
12 (5.2)
12 (4.9)
15 (6.7)
TEAEs leading to drug withdrawal
6 (2.6)
10 (4.0)
6 (2.7)
TEAEs leading to death
1 (0.4)
0 (0)
2 (0.9)
Most common (≥5%) TEAEs
   Weight Increased
17 (7.4)
23 (9.3)
17 (7.6)
   Injection site pain
11 (4.8)
26 (10.5)
9 (4.0)
   Headache
19 (8.2)
13 (5.3)
12 (5.4)
   Nasopharyngitis
10 (4.3)
12 (4.9)
13 (5.8)
Upper respiratory infection
7 (3.0)
17 (6.9)
9 (4)
Most common (≥1%) serious TEAEs
Psychiatric disorders
8 (3.5)
6 (2.4)
7 (3.1)
Schizophrenia
4 (1.7)
4 (1.6)
1 (0.4)
Abbreviation: TEAE, treatment-emergent adverse event.

Observational Analysis

Garcia-Jiménez et al (2026)3 conducted a multicenter, observational, ambispective mirror-image longitudinal study to evaluate the effectiveness and safety of INVEGA HAFYERA in patients with schizophrenia who were previously stabilized on INVEGA SUSTENNA or INVEGA TRINZA in real-world clinical settings.

Study Design

  • The study assessments were conducted at three predefined time points:
    • Baseline: first INVEGA HAFYERA administration
    • 6 months: at the time of the second INVEGA HAFYERA administration
    • 12 months: after 1 year of treatment, corresponding to the third INVEGA HAFYERA administration.
  • Eligible patients were adults (≥18 years) diagnosed with schizophrenia who received stable treatment with INVEGA SUSTENNA or INVEGA TRINZA and initiated INVEGA HAFYERA between October 1, 2022, and September 30, 2023.

Results

Patient Demographics

Selected Baseline Demographic Characteristics – Mirror-Image Analysis3
Characteristic
Patients who Switched to INVEGA HAFYERA
(N=158)
Age, years, mean (SD)
49.9 (11.6)
Age at schizophrenia diagnosis, years, mean (SD)
26.5 (8.3)
Male, n (%)
121 (76.6)
Duration of illness, years, mean (SD)
24.5 (11.3)
Comorbidities, n (%)
86 (54.4)
Prior INVEGA TRINZA use, n (%)
91 (57.6)
Zero hospitalization in prior year, n (%)
137 (86.7)
Sexual dysfunction, n (%)
6 (7.0)
CVRF, n (%)
45 (52.3)
SDS score, mean (SD)
29.1 (6.6)
CGI score, mean (SD)
4.1 (0.9)
Abbreviations: CGI, Clinical Global Impression; CVRF, Cardiovascular Risk Factors; PP3M, paliperidone palmitate once-every-3-months; SD, standard deviation; SDS, Sheehan Disability Scale.
Efficacy Outcomes
  • A total of 158 patients were included at baseline, of which 144 patients were evaluable at 6 months and 131 patients were evaluable at 12 months.
  • The proportion of patients requiring hospitalization decreased at both 6 months (P<0.01) and 12 months (P<0.05) compared with baseline.
    • During follow-up, hospitalization occurred in 8.1% of patients at 6 months and further decreased to 3.1% at 12 months.3
  • CGI and SDS scores decreased from baseline to 6 months and 12 months of follow-up. See Table: Overall Summary of Efficacy Outcomes – Mirror-Image Analysis.3

Overall Summary of Efficacy Outcomes – Mirror-Image Analysis3
Parameter
Baseline (n=158)
6 Months (n=144)
12 Months
(n=131)
Hospitalization (%)
13.3a
8.1
3.1
CGI score, mean (SD)
4.1 (0.9)
3.8 (0.9)
3.7 (0.9)
SDS score, mean (SD)
29.1 (6.6)
26.7 (7.4)
26.5 (7.5)
Antipsychotic monotherapy use, n (%)
53 (33.5)
52 (36.1)
46 (35.1)
Substance use, n (%)
63 (39.9)
52 (36.1)
45 (34.6)
aWithin prior year.Abbreviations: CGI, Clinical Global Impression; SD, standard deviation;
SDS, Sheehan Disability Scale.
Safety Outcomes
  • At 6 months, 32.6% of patients experienced AEs, increasing to 38.2% at 12 months. See Table: Overall Summary of TEAEs – Mirror-Image Analysis.3
    • Two patients in 12 months experienced severe AE, marked increases in cholesterol levels or motor symptoms of sufficient clinical severity to warrant consideration of treatment discontinuation.
  • A total of 4 deaths were reported during the study, none were considered related to INVEGA HAFYERA treatment.3
  • A significant reduction in substance use was observed from baseline to 6 months
    (42.36% vs 36.11%; P<0.01) and to 12 months (40.00% vs 34.62%; P<0.05).3

Overall Summary of TEAEs – Mirror-Image Analysis3
Outcome
6 Months (n=144)
12 Months (n=131)
≥1 AE, n (%)
47 (32.6)
50 (38.2)
Number of AEs, n (%)
   0
97 (67.4)
81 (61.8)
   1
43 (29.9)
43 (32.8)
   2
4 (2.8)
7 (5.3)
Severe AE, n (%)
1 (0.8)
2 (1.5)
Dyslipidemia, n (%)a
30 (75.0)
32 (82.1)
Parkinsonism, n (%)a
18 (38.3)
22 (46.8)
Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event.aPercentages for dyslipidemia and parkinsonism were calculated among patients with AEs.

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
11 June 2026.

 

References

Show
1 Najarian D, Sanga P, Wang S, et al. A randomized, double-blind, multicenter, noninferiority study comparing paliperidone palmitate 6-month versus the 3-month long-acting injectable in patients with schizophrenia. Int J Neuropsychopharmacol. 2022;25(3):238-251.  
2 Correll C, Johnston K, Turkoz I, et al. Comparing two transitioning strategies to paliperidone palmitate once-every-6-months. CNS Spectr. 2024;29 (6):633-639.  
3 García-Jiménez J, Lafuente-Casanova Ó, Salas R, et al. 12-Month mirror study on the effectiveness and safety of six-month paliperidone palmitate in patients with schizophrenia: a multicenter Andalusian cohort (PAPSEM study). Psychiatry Res. 2026;356:116903.  

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