Oryzon Genomics, S.A. announced topline results from the Phase IIb PORTICO trial, evaluating the efficacy and safety of vafidemstat in Borderline Personality Disorder (BPD). Summary of Efficacy Data: A mixed model repeated measures (MMRM) completed on the multiple independent primary endpoints for overall disease as measured by the Borderline Personality Disorder Checklist (BPDCL) and for agitation and aggression by the Clinical Global Impression-Severity focused on Agitation/Aggression (CGI-S A/A) across weeks 8-12 showed for both endpoints a consistent reduction over the values in the placebo group throughout the treatment, which did not reach statistical significance (p = 0.41 and p = 0.25, respectively).  However, statistically significant overall disease improvement was achieved on the secondary endpoint Borderline Evaluation of Severity (BEST) across weeks 8-12 (p = 0.042). The BEST scale was designed to measure BPD symptom severity and adaptive coping responses including negative behaviors and actions such as injuring oneself, thoughts and feelings including mood reactivity, identity disturbance, unstable relationships, paranoia, emptiness, and suicidal thinking, and positive behaviors such as avoidance of self-destructive and/or self-defeating behaviors.

The relative reduction observed in the vafidemstat-treated group over the placebo group was consistent throughout the treatment and reached a maximum of 38% at week 10. Additionally, statistically significant improvement in agitation and aggression as measured by the STAXI-2, Trait Anger (p = 0.026) was also demonstrated across weeks 8-12. The Trait Anger scale (10 items) measures the disposition to experience angry feelings as a personality-like trait over time.

The relative reduction observed in the vafidemstat-treated group over the placebo group was consistent throughout the treatment and reached a maximum of 80% at week 10. It was also encouraging to note that all results favored vafidemstat treatment over placebo across the multiple independent primary and secondary efficacy endpoints. Furthermore, the Global Statistical Test (GST p-values) confirms a strong trend effect across all efficacy endpoints.

GST is designed to globally address whether a treatment is efficacious across different aspects of a condition. The GST efficiently summarizes a global treatment?s effect when the disease is complex and multifactorial. Summary of Safety and Tolerability Data: Vafidemstat was safe and well-tolerated.

Adverse events (AEs) were generally consistent with the safety profile of vafidemstat seen to date, with no new safety findings. The number of subjects with Treatment-Emergent Adverse Events (TEAEs) was slightly lower for those receiving vafidemstat (57.5%) vs placebo (65.4%). Treatment-Related TEAEs were similar between groups (34.0% of subjects in the vafidemstat arm vs 31.7% in placebo).

Those TEAEs leading to Study Discontinuation, Study Drug Withdrawal, or Study Drug Interruption were low overall. Regarding TEAE Severity, the majority were independently assessed by the investigators as Mild (48.1% of subjects in vafidemstat versus 57.7% in placebo) or Moderate (27.4% in vafidemstat versus 33.7% in placebo), with low numbers in both groups experiencing a Severe AE (4.7% in vafidemstat versus 3.8% in placebo). The majority of TEAEs Recovered/Resolved by the end of the trial.

There were no deaths in PORTICO, and the only TEAE with sequelae was on placebo.