Oryzon Genomics has enrolled the first patient in PORTICO, a Phase IIb clinical trial assessing vafidemstat as a treatment for borderline personality disorder (BPD), at the Vall d’Hebrón Hospital in Barcelona, Spain.
The trial is the first of its kind in a real-world BPD population.
Oryzon is a Spanish clinical-stage biopharmaceutical company invested in epigenetics to advance treatments in disease areas with a high unmet need.
PORTICO, a multi-centre, double-blind, randomised, placebo-controlled Phase IIb trial, will evaluate vafidemstat’s efficacy and safety in BPD patients. The trial’s two primary endpoints will be a reduction of aggression and agitation and an overall improvement of BPD symptoms.
Vafidemstat (ORY-2001), one of Oryzon’s leading compounds, is an oral, CNS-optimised LSD1 inhibitor. The molecule has shown promise in a number of neurological disease areas and acts to decrease cognitive impairment, including memory loss and neuroinflammation, and also has neuroprotective effects.
The PORTICO study will include a total of 156 patients, with 78 patients in each arm.
“PORTICO is the first interventional clinical trial in a real-world BPD population, with inclusion and exclusion criteria designed to offer the highest potential for a viable treatment option for BPD patients,” said Oryzon’s Chief Medical Officer for CNS, Dr Michael Ropacki.
“These patients are typically treated off-label with drugs with significant side-effect profiles. Vafidemstat has already proven to be safe and well-tolerated in clinical trials in approximately 300 treated subjects, some on continuous therapy for up to 18 months. Vafidemstat is non-sedating, does not cause unwanted weight gain or produce extrapyramidal side effects. We are excited and hopeful that vafidemstat may provide a safe and effective therapy for BPD patients and allow them the opportunity for a full and productive life.”
The study has started in Europe with the activation of two sites in Barcelona, Spain. Oryzon expects that around 20 sites from Spain, Germany, Bulgaria and the United States will participate in the study. Recruitment is expected to complete in approximately 18 months.
In animal studies, vafidemstat restored memory and reduced the heightened aggressiveness of SAMP8 mice (Senescence-accelerated mouse-prone 8), a model for accelerated ageing and Alzheimer’s disease (AD), to normal levels. The drug also reduced social avoidance and enhanced sociability in rodents.
Oryzon has conducted two Phase IIa clinical trials looking at vafidemstat to treat aggression in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate to severe AD (REIMAGINE-AD). Positive preliminary clinical results were reported in both.
Additional completed Phase IIa clinical trials involving vafidemstat include the ETHERAL trial in patients with mild to moderate AD, where a significant reduction of the inflammatory biomarker YKL40 was observed after six months of treatment, and the pilot, small-scale SATEEN trial in relapsing-remitting and secondary progressive MS.
BPD, now sometimes referred to as emotionally unstable personality disorder, is a psychiatric illness that affects between 0.5% and 1.6% of the general population.
BPD patients experience severe emotional instability, impulsivity, irrational beliefs and distorted sense of self, and the condition is often characterised by intense but unstable relationships with others. Up to 10% of those affected die by suicide.
Psychotherapy is normally the first-line treatment and while medications may be prescribed to treat specific symptoms, there is no dedicated, FDA-approved treatment for BPD.
An estimated 1.4 million BPD patients in the US are being treated with off-label drugs, approved for other conditions that work to manage symptoms rather than the disease itself.
In addition to the recently authorised PORTICO Phase IIb trial in BPD, Oryzon is preparing a Phase IIb trial in schizophrenia patients (EVOLUTION). Vafidemstat is also being explored in a Phase II trial in severe Covid-19 patients (ESCAPE), assessing drug’s capability to prevent acute respiratory distress syndrome (ARDS), one of the most concerning complications of the virus.