ORYZON Presents Final Data From Phase IIb Vafidemstat Trial in BPD at ECNP Congress

Oryzon Genomics, S.A., a clinical-stage biopharmaceutical company focusing on epigenetics to develop treatments for diseases with significant unmet medical needs, has released the final data from its PORTICO Phase IIb trial of vafidemstat, targeting Borderline Personality Disorder (BPD). The results were shared at the New Medications Symposium during the 37th European College of Neuropsychopharmacology (ECNP-2024) congress in Milan, Italy. Dr. Michael Ropacki, Oryzon’s Chief Medical Officer for CNS, presented the findings.

The PORTICO trial was a global, double-blind, randomized, placebo-controlled study extending over 14 weeks. It involved 211 patients split evenly into two groups. The primary objectives were to assess the reduction in agitation and aggression as well as overall disease improvement in BPD severity. Secondary endpoints also focused on these parameters but utilized different scales for measurement. The trial took place across 27 clinical sites, including 14 in the U.S. and 13 in Europe.

Dr. Ropacki expressed optimism about the results, noting that the full data set showed better outcomes compared to the initial results released in January 2024. He emphasized the potential of vafidemstat to provide a novel treatment option for BPD with an epigenetic mechanism-of-action that avoids the side effects common with current off-label treatments. The findings indicate significant reductions in agitation and aggression and overall disease improvement, suggesting vafidemstat could substantially improve the quality of life for BPD patients and their communities.

Dr. Carlos Buesa, Oryzon’s CEO, highlighted the significance of PORTICO, mentioning that this is the first large, randomized Phase IIb trial in BPD to achieve statistical significance. The study demonstrated meaningful improvements, and vafidemstat appeared to have a holistic effect on the disease. Following a recent End-of-Phase II meeting with the FDA, a positive response could lead to the immediate preparation for a Phase III trial, potentially making Oryzon the only company with a Phase III drug in development for BPD, a condition with no FDA-approved treatments.

Key highlights of the trial data include a substantial and statistically significant reduction in agitation and aggression as measured by the STAXI-2 Trait Anger scale, with a p-value of 0.0071 across Weeks 8–12. The vafidemstat-treated group experienced a maximum relative reduction of 92.1% in agitation and aggression at Week 10. The BEST scale, measuring overall BPD severity, also showed improvement, with a p-value of 0.0260 across the same period. While primary endpoints showed improved p-values, they did not reach statistical significance. However, there was a notable trend of improvement in depression symptoms measured by the BDI-II Total Score.

The T-Forest plot analysis confirmed that vafidemstat performed better than placebo across all primary and secondary efficacy endpoints. The Global Statistical Test (GST) indicated a significant global treatment effect favoring vafidemstat, with a p-value of 0.0362. Vafidemstat was found to be safe and well-tolerated, with adverse events consistent with its known safety profile and no new safety concerns.

Oryzon intends to move forward with a Phase III study contingent on FDA feedback. The company emphasizes the economic potential of vafidemstat, with recent grants and notifications from multiple Patent Offices highlighting its unique position in the market.

In conclusion, the PORTICO trial's final results suggest that vafidemstat could provide a groundbreaking treatment option for BPD, addressing a critical unmet need in the field of mental health.