ORYZON presents the final data from PORTICO, a global Phase IIb vafidemstat trial in Borderline Personality Disorder (BPD), at the European College of Neuropsycopharmacology (ECNP) congress

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced that it will present today the final data from its Phase IIb PORTICO trial of vafidemstat in patients with Borderline Personality Disorder (BPD) as an oral presentation at the New Medications Symposium, a special symposium focused on clinical trials of new compounds within the 37th European College of Neuropsychopharmacology (ECNP-2024) congress, which is currently being held in Milan (Italy). Oryzon’s oral presentation, titled "Final results: Phase 2b PORTICO Study: Efficacy of Vafidemstat in Borderline Personality Disorder", will be delivered by Dr. Michael Ropacki, Oryzon’s Chief Medical Officer for CNS. In addition to the oral presentation, the results will also be presented as a poster at ECNP-2024. 

PORTICO (EudraCT No.: 2020-003469-20, ClinicalTrials.gov Identifier NCT04932291) was a global double- blind, randomized, placebo-controlled, adaptive 14-week Phase IIb trial evaluating the efficacy and safety of vafidemstat at 1.2 mg/day in a BPD population. The study recruited a total of 211 patients, randomized 1:1 in two arms. The trial had two independent primary endpoints: reduction of agitation and aggression and overall disease improvement in BPD severity. In the absence of a well-established regulatory endpoint, the trial also included two secondary endpoints also exploring the reduction of agitation and aggression and overall disease improvement in BPD severity by different scales. PORTICO included a total of 27 clinical sites, 14 in the U.S. and 13 in Europe (Germany, Spain, Bulgaria, and Serbia).

Dr. Michael Ropacki, Oryzon’s Chief Medical Officer for CNS stated, “The PORTICO results are exciting and extremely promising in several ways. These full results are improved compared to the topline results shared in January 2024. BPD is a serious mental health disease with great interpersonal, social, and economic burden and vafidemstat potentially proposes a novel treatment option with an epigenetic mechanism-of- action that does not have the side-effect baggage of current off-label treatments. The significant and clinically meaningful reductions in agitation and aggression as well as overall disease improvement produced by vafidemstat offer the first potential pharmacologic treatment to significantly improve the lives of BPD patients and those around them.”

Dr. Carlos Buesa, Oryzon’s CEO added: “PORTICO marks a significant milestone in BPD research, as this is the first time, to our knowledge, that statistical significance was achieved in a large, randomized Phase IIb trial in BPD. Our study demonstrated meaningful improvements, and vafidemstat seems to produce a holistic effect in the disease. In a recent End-of-Phase II meeting with the FDA we had the opportunity to discuss these results. A positive response from the FDA would trigger immediate preparations of our PORTICO-2 Phase III trial, and would make Oryzon the first, and only, company with a drug in Phase III clinical development in BPD, an indication with a huge unmet medical need and no drugs approved. The recent grants or intention-to-grant notifications for vafidemstat’s patents in BPD and aggression received from different Patent Offices highlight the economic potential of this unique program.”

Presentation Data Highlights:

The final data show a significant overall improvement compared to the preliminary top-line data (TLD) released in January.

• Notably, the agitation and aggression of patients, as measured by the secondary endpoint STAXI-2 Trait Anger scale, showed a substantial, statistically significant, and clinically meaningful reduction in the vafidemstat arm compared to placebo, with a p-value of 0.0071 across Weeks 8–12 (previously p = 0.0259). The relative reduction in the vafidemstat-treated group over the placebo group reached a maximum of 92.1% at Week 10, with an average reduction of 58.6% across Weeks 8–12 (previously 80.8% and 46.7%, respectively).
• Additionally, the secondary endpoint Borderline Evaluation of Severity (BEST), an overall measure of BPD severity, also showed an improvement compared to TLD, with a p-value of 0.0260 across Weeks 8–12 (previously p = 0.0423). The maximal relative reduction in the vafidemstat-treated group over the placebo group reached 38.9% at Week 10, with an average reduction of 30.9% across Weeks 8–12.
• The p-values for the primary endpoints (CGI-S A/A and BPDCL) also improved compared to the preliminary TLD, but did not reach statistical significance.
• Interestingly, a trend of improvement in depression measured by the BDI-II Total Score by Weeks 8–12 was detected (p= 0.0944 ), with an average reduction over the placebo group of 42.2% across Weeks 8–12.
• The T-Forest plot analysis showed that all results continued to consistently favor vafidemstat treatment over placebo across all primary and secondary efficacy endpoints.
• Notably, the final analysis confirmed now a global treatment effect favoring vafidemstat by the Global Statistical Test (GST), with the GST p-value showing a statistical significance, particularly when considering global improvement in the severity of the disease and in agitation/aggression (p= 0.0362, previously a strong trend). The GST is designed to assess whether a treatment is effective across different aspects of a condition, efficiently summarizing the overall treatment effect, especially when dealing with complex, multifactorial diseases.
•  Vafidemstat was, as in all previous clinical studies, safe and well-tolerated. Adverse events (AEs) were generally consistent with the safety profile of vafidemstat seen to date, with no new safety findings. Treatment-Emergent Adverse Events (TEAEs) were slightly lower in those receiving vafidemstat (57.5% vs 65.4% in the placebo group), though Treatment-Related TEAEs were similar between groups.
• An observation of interest was that vafidemstat-treated patients showed a reduced inclination towards self-harm compared to the ones receiving placebo (1 patient vs 6 patients in the placebo group).

All these data have been presented to the FDA in an end-of-Phase II meeting held recently to discuss a registrational Phase III study for the treatment of BPD.

A copy of the ECNP presentation is available here and the accompanying poster is available here.