Oryzon Genomics has achieved a significant milestone with the publication of final Phase IIa REIMAGINE trial results for vafidemstat in Psychiatry and Clinical Neurosciences, demonstrating the drug's potential in treating agitation and aggression across multiple psychiatric conditions.
Breakthrough in Psychiatric Treatment
The innovative basket trial evaluated vafidemstat, an oral LSD1 inhibitor, in adult patients with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD). Participants received 1.2 mg/day of vafidemstat over an 8-week period, with results showing significant reduction in agitation and aggression across all patient groups.
"This innovative study, one of the first basket trials in CNS, was the first to demonstrate that targeting LSD1 is a safe and entirely novel mechanism of action for managing agitation/aggression in psychiatric disorders," stated Dr. Jordi Xaus, Oryzon's CSO.
Clinical Impact and Safety Profile
The trial demonstrated that vafidemstat was not only safe and well-tolerated but also produced meaningful improvements in non-aggressive features and overall disease indicators. These positive outcomes have laid the groundwork for expanded development in psychiatric indications.
Dr. Carlos Buesa, Oryzon's CEO, emphasized the drug's potential: "Successfully mitigating agitation and aggression could significantly improve BPD patients' daily lives. If the upcoming Phase III trial yields positive results, vafidemstat could be further explored for broader applications in controlling aggression across other CNS disorders."
Advancing to Phase III Development
Following these promising results, Oryzon conducted the Phase IIb PORTICO trial in BPD, where vafidemstat showed nominal statistical significance in reducing agitation and aggression on the STAXI-2 Trait Anger scale and improving overall BPD disease on the BEST scale. The company has received positive feedback from the FDA in an End-of-Phase II meeting and is now preparing the protocol for the PORTICO-2 Phase III trial.
Broader Applications and Ongoing Research
Vafidemstat's development program extends beyond BPD, with ongoing evaluation in the Phase IIb EVOLUTION trial for negative symptoms of schizophrenia. The drug's mechanism of action suggests potential applications across various CNS disorders, supported by preclinical studies showing effects on cognitive impairment, neuroinflammation, and neuroprotection.
The publication of these results marks a crucial step forward in psychiatric medicine, offering a potential new treatment option for managing aggressive behaviors in multiple psychiatric conditions. As Oryzon advances toward Phase III trials, the medical community awaits further validation of this novel therapeutic approach.
