Injection site reactions and local tolerability with subcutaneous long-acting injectable olanzapine (TV-44749) in schizophrenia: phase 3 SOLARIS trial results

Background

Long-acting injectable antipsychotics (LAIs) have demonstrated improved clinical outcomes, better adherence, and reduced mortality risk in schizophrenia; however, injection site reactions (ISRs) could contribute to treatment discontinuation. TV-44749 is an innovative, investigational, subcutaneous LAI formulation of olanzapine. The Phase 3 SOLARIS trial (NCT05693935) evaluated efficacy, safety, and tolerability of TV-44749 as a treatment for adults with schizophrenia. Results showed significantly greater efficacy with TV-44749 versus placebo and a systemic safety profile consistent with other approved olanzapine formulations in adults with schizophrenia. This analysis characterizes ISRs and local tolerability associated with TV-44749 in the SOLARIS trial.

Methods

SOLARIS consisted of an 8-week, randomized, double-blind, placebo-controlled period followed by a ≤48-week, open-label safety period. In this analysis, ISRs and local tolerability were evaluated across the SOLARIS integrated trial periods of ≤56 weeks in patients who received ≥1 dose of once-monthly TV-44749 (318, 425, or 531 mg). ISRs and local tolerability (presence of erythema, induration/swelling, and pain) were periodically and proactively assessed after each injection, including numeric pain rating scale scores and size-based grading. Incidence was calculated by injection, with the total number of patients receiving the injection as the denominator.

Results

ISRs were observed in 30% (180/604) of patients, most frequently injection site induration (12%), pain (12%), and erythema (10%). ISR frequency decreased with successive injections, with an incidence of 24% (146/604) after the first injection, 14% (69/492) after the second, 6% (22/378) after the third, and continuing to decrease until stabilizing at ≈2% after the seventh and subsequent injections. ISRs led to discontinuation in 2% (10/604) of patients. ISRs were most commonly mild (21% [125/604]) or moderate (8% [50/604]) in severity; severe ISRs were reported in 5 (<1%) patients. Treatment initiation local reactions are a subset of ISRs that present with local inflammation and occur within the first 4 injections. These reactions were reported in 7% (42/604) of patients, mainly after the first injection (6% [39/604]), with an incidence <1% thereafter. They followed a transient, self-limiting course, without systemic involvement and with minimal recurrence, and led to discontinuation in 1% (8/604) of patients. Local tolerability findings of erythema and induration/swelling were absent for most patients for all post-injection assessments, including 94% (564/604) and 76% (459/604) of patients, respectively, at 3 hours after the first injection, and 92–97% and 75–84% of patients, respectively, after subsequent injections. When present, erythema and induration/swelling were generally minimal across all assessments. Most patients reported no pain after each injection, including 76% (458/604) and 83% (497/604) of patients at 30 minutes and 3 hours, respectively, after the first injection, 77% (173/226) and 85% (193/226), respectively, after the sixth injection, and 77% (113/146) and 92% (134/146), respectively, after twelfth injection. Pain ratings decreased in incidence and severity with successive injections. When pain was present, ratings were generally low and transient.

Conclusions

In SOLARIS, ISRs with TV-44749 were predominantly mild or moderate in severity, occurred most frequently early in treatment, and declined with successive injections. Findings support TV-44749 as a well-tolerated treatment in adults with schizophrenia.

References

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