Oryzon Genomics, S.A. has announced that it received official minutes from its End-of-Phase II meeting with the U.S. Food and Drug Administration (FDA) regarding vafidemstat for the treatment of Borderline Personality Disorder (BPD). The FDA's feedback supports Oryzon's plan to move forward with preparing a full PORTICO-2 Phase III trial protocol for submission and study approval.
The End-of-Phase II meeting, held in late August, involved a thorough evaluation of vafidemstat's development plan, including preclinical data, toxicology, clinical pharmacology, and clinical studies. The meeting minutes confirmed alignment between Oryzon and the FDA on key elements of the PORTICO-2 Phase III clinical trial design.
Key Points from the FDA Meeting
Several significant points emerged from the meeting:
- The FDA acknowledged that agitation-aggression in BPD has the potential to be an acceptable target indication.
- Oryzon may pursue a Phase III study using the STAXI-2 Trait anger scale as a primary efficacy endpoint measure. However, the company will need to provide additional information to demonstrate that STAXI-2 Trait anger is a clinically meaningful endpoint in BPD patients, potentially through a Qualitative Research of the scale.
- Secondary endpoints will include patient-rated and clinician-rated scales, such as CGI-S A/A to assess agitation/aggression, and BEST and CGI-S to assess overall BPD improvement.
- A Qualitative Research Study will be conducted with a subset of PORTICO-2 patients to further validate the proposed endpoints. The Qualitative Study protocol will be submitted for FDA review and feedback before initiation.
- Oryzon plans to provide the psychometric properties and performance data for the selected primary and key secondary endpoints for FDA review before starting the Phase III study.
- The estimated total sample size for the PORTICO-2 Phase III study is 350 patients, randomized 1:1 to either vafidemstat or control, with a total trial duration of 18 weeks.
- Subject to FDA review of the final data, the PORTICO-2 Phase III study has the potential to be one of the two registrational trials required by the FDA.
Promising Phase IIb Results
Data from the Phase IIb PORTICO study, which used the STAXI-2 Trait anger scale to assess agitation-aggression in BPD, demonstrated a nominally significant and clinically meaningful reduction of agitation and aggression in the vafidemstat group compared to placebo (FAS analysis, p=0.0071). The vafidemstat group showed a 58.6% relative reduction over the placebo group at weeks 8-12, with p-values at weeks 10 and 12 of p=0.006 and p=0.016, and relative reductions over the placebo group of 92.1% and 57.1%, respectively.
Management Commentary
Carlos Buesa, CEO of Oryzon, stated, "We are thrilled with the positive outcome of our interactions with the FDA and the prospect of advancing vafidemstat into pivotal Phase III clinical studies for BPD, an area with a significant unmet medical need, as no approved drugs currently exist."
Michael Ropacki, Oryzon’s CMO for CNS, added, "These clinically meaningful reductions in agitation/aggression and overall disease improvement seen with vafidemstat strongly support its potential as a pharmacological treatment for BPD, with the promise to significantly improve the lives of BPD patients and their families."
Next Steps
Oryzon will now begin preparations for the Phase III program, including finalizing the PORTICO-2 Phase III trial protocol for submission to the FDA. The company also plans to engage with European regulatory agencies before initiating the Phase III trial.
About Borderline Personality Disorder
Borderline Personality Disorder (BPD) affects between 0.5 and 1.6% of the general population. BPD is characterized by emotional instability, impulsivity, irrational beliefs, distorted perception, and unstable relationships. It is estimated that around 1.4 million BPD patients in the U.S. are being treated with off-label drugs, as there are currently no FDA-approved treatments for BPD.
