2026 ECNP Congress

PS04-4236

Do cultural factors and language influence efficacy outcomes? Results from Study 008A in Latin America and Asia

Ravi Anand — A. Turolla, G. Chinellato, F. Sansi, G. Bianchi, R. Hartman · Anand Pharma Consulting, Pharmaceutical R&D, St.Moritz, Switzerland

2026 ECNP Congress

Introduction

Lines of evidence suggest that the results from CNS clinical trials evaluating new chemical entities are strongly influenced by the cultural and religious context, patient background, and language used to assess participants [1,2]. For instance, antipsychotic (AP) trials conducted in India are thought to provide greater efficacy signals potentially due to background factors, religious biases, caregiver structure, and bias towards overrating of severity [3]. Additionally, evidence from cross-cultural, longitudinal studies suggests better outcomes for patients in developing countries compared with those in developed ones, possibly reflecting greater social integration and more supportive family structures in the former [4].

Aims

To assess the influence of cultural background and language on results from evenamide add-on study 008A [5], performed in multiple countries and ~20 languages in patients who are inadequate responders to second generation antipsychotics (SGA), including clozapine.

Methods

Study 008A was a phase 3, 4-week, randomized, double-blind, placebo-controlled trial that determined the efficacy and safety of evenamide 30 mg bid as add-on in patients with schizophrenia poorly responding to an SGA (including clozapine). Plasma levels were measured before baseline to assess patients’ adherence to their background SGA. The study was conducted in 11 countries across Asia, Latin America, and Europe. A post-hoc analysis was conducted to evaluate the difference in background characteristics and efficacy in the populations enrolled in Latin America (Latam) and in Asia (India) compared to that enrolled in other countries.

Results

Compared with patients enrolled in other regions, Indian patients were younger (~36 y.o.) while those enrolled in Latin America were older (~43 y.o.); 10% more males were enrolled in India compared to other regions. A significantly higher proportion of patients lived with their family in India (93%) and Latam (92%). The duration of illness and that of AP treatment was significantly shorter in Indian patients; accordingly, these latter had a markedly lower number of prior psychiatric hospitalizations.

At baseline, the mean PANSS total score and the CGI-S score were significantly lower in Indian patients compared to the rest-of-world (RoW), while a statistically significant greater CGI-S baseline score was observed in the Latin American population (~4.8 vs ~4.5 in RoW). Statistically significant improvements were noted on the PANSS Total and Positive subscale in all regions, with the greatest drug-placebo difference observed in Latam (-4.8 vs -2.3 in RoW). A significant benefit was also observed on the CGI-S in India, and on the PANSS General Psychopathology in Latam. The proportion of patients with any improvement on the CGI-C was significant in India. Conversely, a significant proportion of responders on the PANSS (≥20% improvement) was noted in Latam.

Conclusions

The primary outcome measure in Study 008A was statistically significant in favour of evenamide when considering the single regions of Latin America and Asia; this suggests that similar cultural background and common clinical practices within each region may have contributed to achieve significant separation between the effects of the active drug and the placebo.

References

  1. Laughren TP. A Growing crisis in schizophrenia drug development: failing signal detection at North American and other clinical trial sites. J Clin Psychiatry. 2020;81(2):19com13110.
  2. Zielen S, Crawford T, Benatti L et al. Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. The Lancet Neurology, 23, 871-882
  3. Kalra G, Bhugra D, Shah N. Cultural aspects of schizophrenia. Int Rev Psychiatry. 2012 Oct;24(5):441-9. doi: 10.3109/09540261.2012.708649
  4. Sartorius N, Shapiro R, & Jablensky A. (1974). The international pilot study of schizophrenia. Schizophrenia Bulletin, 1(11), 21–34. https://doi.org/10.1093/schbul/1.11.21
  5. Anand R, Turolla A, Chinellato G, Sansi F, Roy A, Hartman R. Efficacy and safety of evenamide, a glutamate modulator, added to a second-generation antipsychotic in inadequately/poorly responding patients with chronic schizophrenia: Results from a randomized, double-blind, placebo-controlled, phase 3, international clinical trial. Neuropharmacology 2025. 266:110275. doi: 10.1016/j.neuropharm.2024.110275