ORYZON Receives FDA Minutes from End-of-Phase II Meeting on PORTICO-2 Phase III Vafidemstat Trial in BPD

Oryzon Genomics, S.A., a clinical-stage biopharmaceutical company specializing in epigenetics, has received positive feedback from the U.S. Food and Drug Administration (FDA) regarding the development of vafidemstat for treating Borderline Personality Disorder (BPD). Following a comprehensive End-of-Phase II meeting, Oryzon is preparing to initiate a Phase III trial, known as PORTICO-2, to further assess the efficacy of vafidemstat.

The FDA meeting in late August 2024 provided crucial insights into multiple aspects of vafidemstat’s development, including preclinical data, toxicology, clinical pharmacology, and clinical studies. Key points confirmed by the FDA include the potential for agitation-aggression in BPD as a target indication and the suitability of using the STAXI-2 Trait anger scale as a primary efficacy endpoint. However, additional information must be provided to validate STAXI-2 Trait anger as a clinically meaningful measure.

The Phase III trial will include secondary endpoints such as patient-rated and clinician-rated scales to assess agitation/aggression and overall BPD improvement. To ensure comprehensive validation, Oryzon will conduct a Qualitative Research Study with a subset of PORTICO-2 patients. The total sample size for the trial is estimated at 350 patients, with an 18-week duration.

The PORTICO-2 Phase III trial is poised to be a pivotal study, potentially serving as one of the registrational trials required by the FDA. Evidence from the Phase IIb PORTICO study demonstrated a significant reduction in agitation and aggression using the same primary endpoint scale, reinforcing the potential efficacy of vafidemstat in BPD treatment.

Oryzon's CEO, Carlos Buesa, emphasized the promising prospects for vafidemstat, highlighting its safety and tolerability demonstrated in earlier trials. He expressed optimism about advancing vafidemstat into Phase III trials for BPD, a condition with significant unmet medical needs due to the lack of FDA-approved treatments. Michael Ropacki, Oryzon’s Chief Medical Officer for CNS, echoed this sentiment, noting the clinically meaningful improvements observed in the reduction of agitation/aggression during the PORTICO Phase IIb trial.

As Oryzon moves forward with the Phase III preparations, it will also engage with European regulatory agencies to align on trial protocols and approvals. The company aims to leverage the robust data collected so far to establish vafidemstat as a viable pharmacological treatment for BPD.

Oryzon Genomics, headquartered in Madrid and Cambridge, Mass., was founded in 2000 and has become a leader in the field of epigenetics. The company focuses on personalized medicine, with a portfolio that includes two LSD1 inhibitors: vafidemstat for CNS disorders and iadademstat for oncology. Oryzon holds a strong position in biomarker identification and target validation, making significant strides in addressing various malignant and neurological diseases.

The PORTICO Phase IIb trial, a global, double-blind, randomized, placebo-controlled study, evaluated vafidemstat's efficacy and safety in BPD patients. The trial's outcomes, presented at the 37th European College of Neuropsychopharmacology congress, showed statistically significant improvements in reducing agitation and aggression, as well as overall disease severity.

Vafidemstat has shown promise beyond BPD, including potential benefits in treating Alzheimer's disease, multiple sclerosis, and severe COVID-19. With a comprehensive clinical development strategy, Oryzon is exploring vafidemstat's application across a range of neuropsychiatric and neurodevelopmental disorders.

Borderline Personality Disorder is a severe psychiatric condition affecting a significant portion of the population, characterized by emotional instability and impulsivity. Despite the high prevalence and impact, no FDA-approved treatments currently exist, making Oryzon's work with vafidemstat highly significant.